The cytoprotective stable gastric pentadecapeptide BPC 157, by its effects, might combine the brain–gut and gut–brain axes’ function ^{[1][2][3][4][5][6]}[1,2,3,4,5,6] in a particular way using its particular capabilities: cytoprotection [7] as a particular vascular effect [1], wound healing [8], and neuroprotection [9]. These were implemented in the most recently reviewed particular effects of the pentadecapeptide BPC 157 on the prompt activation of the vascular collaterals and counteraction of the occlusion/occlusion-like syndromes in rats with permanent major vessel occlusions and similar procedures severely disabling endothelium function, both peripherally and centrally, causing muscle disturbances in both striated and smooth muscles, disabling heart failure recovery as a whole ^[1][2][6][7][1,2,6,7]. Thus, these most recent findings ^[1][2][6][7][1,2,6,7] may readdress the particular issue of the brain–gut axis and gut–brain axis, using the original conceptual marks long ago proposed, starting with the gut peptides ^[10][11][12][10,11,12].

2. Behavior

In general, the potential holding of the behavioral disturbances and therapeutic effects of the agents, such as BPC 157, with logistical assistance from the many essential systems (i.e., GABA, opioids, dopamine, serotonin, and NO system) ^[5][9][5,9] largely implemented in physiology and pathology, might have been an indicative link for possible significances and therapies. On the other hand, it might spark a fierce controversy between the value of animal models and their potential translations to the human condition ^[13][87]. This might have been the case with some particular modulatory effects of BPC 157 therapy. They might have been particularly presented and commonly applicable when these systems might have been disabled in either way [5]. The above-mentioned particular modulatory effects, encompassing the entire NO system ^[14][69], may be a particular illustration of a complex effect that regularly resolves activity. First, BPC 157-induced NO is released on its own ^[15][16][17][60,70,71], which may be resistant to N(G)-nitro-L-arginine methylester (L-NAME)-induced NO synthase (NOS) inhibition. Then, there is a counteraction of NO synthase (NOS) inhibition (i.e., L-NAME-hypertension and pro-thrombotic antagonized effects may be particular examples) ^[16][18][43,70]. Finally, NO over-stimulation was also antagonized (antagonization of L-arginine-hypotension and anti-thrombotic, pro-bleeding effects may provide indicative examples) ^[16][18][43,70]. Likewise, the counteraction of the isoprenaline myocardial infarction by BPC 157 therapy might include a NO effect ^[19][57]. Given the BPC 157–dopamine–NO system interaction (i.e., BPC 157 therapy might antagonize L-NAME-induced catalepsy) ^[20][88], such an interaction might support the hypothesis that BPC 157 therapy might exert two seemingly opposite effects. It might consistently antagonize the effect of the dopamine receptors’ blockades as well as antagonize the effect of the dopamine receptors’ agonization/over-stimulation ^{[20][21][22][23][24]}[88,89,90,91,92]. With these caveats, the evidence concerning the particular beneficial effects of BPC 157 therapy (anxiolytic; anticonvulsive; antidepressant; catalepsy counteraction, which might have been used in positive and negative schizophrenia symptom models) within the brain–gut axis implementation (i.e., simultaneous effect, centrally and peripherally) will be presented. A particular anxiolytic effect appeared with the antagonization of the most serious side effects of benzodiazepine therapy, the development of tolerance, and physical dependence, all of which were attenuated ^[23][91]. Illustratively, a later, acute administration of diazepam together with convulsant demonstrated a BPC 157-attenuated diazepam tolerance. The later administration of isoniazid evidenced the antagonization of a postponed physical dependence/withdrawal effect ^[23][91]. Therefore, it might have been a particular anxiolytic effect (i.e., not burying and no more shocks (shock probe/burying) and a greater number of crossing and exploratory rearing behaviors in a dark areas (light/dark test)) ^[25][93]. In addition, this effect might affect general anesthesia as well ^[26][94] (i.e., BPC 157 antagonized thiopental-induced general anesthesia (parallel shift of the dose–response curve to the right) ^[26][94]). In this, illustrative of the antagonization of ethanol disorders, BPC 157 was suggested to act as an antagonist of ethanol ^[27][28][85,95], counteracting both acute and chronic alcohol intoxications ^[29][30][96,97]. Furthermore, such an antagonization might have been a particular point given to anesthetic barbiturates, such as thiopental, and the counteraction of their activities as both agonists at GABAA receptors and enhancers of receptor responses to GABA ^[31][98]. Additionally, BPC 157 exhibited an intrinsic anti-convulsive activity and counteracted convulsions induced by picrotoxin, isoniazid, and bicuculline ^[23][32][91,99], known as the non-competitive blocker of GABA-receptor chloride channels, the inhibitor of glutamic acid decarboxylase and GABA-synthesis, or the GABAA antagonist ^[33][34][35][100,101,102]. Thus, BPC 157 might act to favor the natural homeostasis of the GABA receptor complex as well as to enhance GABAergic transmission. In addition, there was an additional anxiolytic effect in the counteraction of negative schizophrenic symptoms in rats dosed with ketamine ^[36][103]. Importantly, these effects were shown to be related to the NO system effects as well ^[26][36][94,103]. Finally, the full complexity of the brain–gut axis function might have been illustrated with the application of alcohol and the extent of the antagonization disturbances. The counteraction included behavioral disturbances in acute and chronic alcohol intoxications ^[29][30][96,97]. Additionally, those counteracted were hypothermia, mucosal and endothelial lesions, liver injuries, and portal hypertension ^{[16][29][30][37][38][39][40]}[70,82,96,97,104,105,106]. Moreover, an additional illustration of both the extensive lesions and BPC 157 therapy potentials appeared in absolute alcohol intragastric administration, producing severe occlusion/occlusion-like syndrome. BPC 157 therapy, as a part of the counteraction of the severe vessel and multiorgan failure syndrome with the activation of the collateral rescuing pathway of the azygos vein (direct blood flow delivery), counteracted brain, lung, liver, kidney, and gastrointestinal lesions; progressive thrombosis, both peripherally and centrally; and, in particular, heart failure, arrhythmia, and infarction ^[37][82]. As an instant effect, those counteracted were intracranial (superior sagittal sinus) hypertension, portal and caval hypertensions, and aortal hypotension. The development of serotonin syndrome belongs to the most serious side effects of antidepressant therapies. BPC 157 therapy might fully counteract serotonin syndrome ^[41][107]. Namely, the irreversible monoamine oxidase (MAO) inhibition (i.e., pargyline) and subsequent serotonin substrate (L-tryptophan as a serotonin precursor) induced fore paw treading, hind limbs abduction, wet dog shake, and hypothermia followed by hyperthermia in rats, which commonly occur in serotonin syndrome ^[41][107]. Both temperature and behavioral changes in all these experiments were counteracted by gastric pentadecapeptide BPC 157. This effect may have been a particular effect, as BPC 157 counteracted each part of the serotonin syndrome presentations. First, BPC 157 therapy counteracted serotonin syndrome initiation (i.e., counteracted pargyline effect) ^[41][107]. Then, in particular, BPC 157 counteracted the full serotonin syndrome crisis (attenuated the adverse effect of the subsequent L-tryptophan application) ^[41][107]. Thus, BPC 157 had a special effect. It was not acting as a serotonin substrate, nor was it able to induce serotonin syndrome (as did L-tryptophan). 

Finally, the evidence that the gut produces 95% of the serotonin in the human body ^[42][65] might illustrate the full complexities of the serotonin system’s brain–gut axis function and the gut–brain axis, likely also related to the effects of BPC 157. BPC 157 in the gastrointestinal tract reduced the release of enteric serotonin and suppressed intestinal motility ^[42][65]. These were along with the increase in the survival rate of cultured enteric neurons and the proliferation of cultured enteric glial cells. 

For the interaction of BPC 157 and dopamine ^[5][9][5,9], common clarification and recovery of the dopamine agents’ adverse effects as novel common points might have been particularly interesting. Namely, they are in a class of psychotropic medications, primarily used either to manage psychosis and bipolar disorder (along with mood stabilizers) ^[43][44][116,117] or as central nervous stimulants in the treatment of attention deficit disorder, narcolepsy, and obesity ^[45][46][118,119]. An ideal agent would be able to affect the dopamine system’s function and cause a therapeutic effect only at the site of a pathologic brain–gut axis and/or gut–brain axis function. In this, BPC 157 may have a complex therapeutic effect. BPC 157 largely interacts with the dopamine system ^[5][9][5,9] since BPC 157 had counteracted various behavioral disturbances, tremors, akinesia, and catalepsy as well as stereotypies that appear within the dopamine system’s disability, its function either reduced or over-amplified ^{[20][21][22][24]}[88,89,90,92]. First, the particular points were the destruction of the brain’s dopamine areas, vesicle depletion, and the blockade of the dopamine receptors. BPC 157 therapy had counteracted disturbances caused by the application of the parkinsongenic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydrophyridine (MPTP) and vesicle depletion by reserpine application ^[47][120]. Second, to emphasize the opposite over-activity disturbances and the complexities of the likely important modulatory role of BPC 157 in dopamine–BPC 157 interactions, BPC 157 counteracted disturbances (i.e., stereotypies) in acute and chronic amphetamine applications (i.e., tolerance and reverse tolerance) ^[22][24][90,92]. Additionally, BPC 157 therapy had antagonized disturbances that were characteristic in the course of the amphetamine, methamphetamine, apomorphine, and dopamine (over)-stimulation in the suited models of the positive-like schizophrenia symptoms ^[20][88].  Furthermore, the involvement of the dopamine system in the full complexities of the brain–gut axis function and the gut–brain axis might have been illustrated with Szabo dopamine anti-parkinsonian agents as a therapy for peptic ulcers ^[48][49][19,138] and, therefore, dopamine agonists in peptic ulcer therapy to counteract duodenal ulcer recidives ^[50][139]. At a particular point, both schizophrenia and the diminished risk for duodenal and gastric ulcers were claimed together ^[51][140]. These also illustrated the evidence that dopamine antagonists alone might produce gastric ulcers ^[52][53][141,142], which dopamine agonists or BPC 157 therapies might have antagonized, but not standard anti-ulcer agents ^[16][54][55][70,121,123].  There might also be a further indicative key focus to indicate the particular potential of BPC 157 as an acting modulator. This might have been the counteracting of its behavioral supersensitivity to the amphetamine-stimulating effect. In principle, the increased amphetamine-climbing behavior following a dopamine antagonist haloperidol application was confirmation of the striatal dopamine receptor up-regulation and the subsequent development of amphetamine supersensitivity ^[56][57][58][143,144,145]. Illustratively, in mice pretreated with haloperidol, and, subsequently, challenged with amphetamine ^[22][90], using the described procedure ^[56][143], this pentadecapeptide antagonized increased climbing behavior ^[22][90]. This might verify the fully avoided striatal dopamine receptors’ up-regulation and supersensitivity ^[22][90].  Furthermore, BPC 157’s special vascular effect (activation of the collateral pathway) [1] might have been an additional clarification of the involvement of the full complexities of the brain–gut axis function together with the gut–brain axis function. As indicated before for the counteraction of absolute-alcohol-intragastric-administration-induced occlusion/occlusion-like syndrome with the activation of the collateral pathway (azygos vein direct blood flow delivery) ^[37][82], BPC 157 therapy may, in the same particular way, counteract the occlusion/occlusion-like syndrome induced with lithium, which is known to interact with dopamine and serotonin systems and is a prototypic agent in bipolar disorder therapy ^[59][56]. 

3. Muscle

The BPC 157 muscle–brain perception ^[5][9][5,9] might depart from the original brain–gut axis’s perception explained with gut peptides and smooth muscles [10]. As a complex whole, the motile system of the gastrointestinal tract (i.e. having several organizational levels) and central nervous system effects (i.e. to centrally modulate the long pathway reflexes traveling in the main vagosympathetic trunks) [10] occurred in the original gut peptides’ perception of the brain–gut axis function. Thus, the gut peptide effect accordingly occurred as part of the brain–gut functioning system. However, such contention about the gastrointestinal–smooth muscle–brain relation [10] might have been insufficient since it lacks consideration of the effects on the striated muscle’s healing and function. Namely, there are several important points providing the peptide agent’s activity consistently considered for muscle healing and function to be also revealed in the general term of the realization of brain-gut axis and gut-brain axis functioning ^[5][9][5,9]. Evidently, any purposive movement requires the impulses to pass from the motor cortex via the spinal cord to the appropriate muscles. Likewise, the impulses passing through various parts of the brain, sending messages back to the motor cortex ^[5][9][5,9], evidence the movement pattern as a highly coordinated event. On the other hand, in this more extensive way for the brain-gut axis and gut-brain functioning, just with the BPC 157 therapy, implementing cytoprotection (simultaneous healing of different tissues, i.e. brain and periphery) ^[2][6][2,6]. Commonly, these may be the general terms of the realization of the brain-gut axis functioning ^[2][6][2,6]. With the BPC 157 therapy the described improved purposive movement rationale (via the motor cortex -spinal cord—appropriate muscles and vice versa) might conceptualize in the brain–muscle axis and muscle–brain axis bidirectional functioning the healing and function recovery of the myotendinous junction (dissection) ^[60][50], the muscle lesion (transection, contusion, and corticosteroid application), and nerve (transection) ^{[60][61][62][63][64][65]}[50,150,151,152,153,154]. With muscle weakness, these might perceive both prime (i.e. brain) and secondary (muscle weakness) injury, prime lesion→secundary lesion, given the muscle weakness as part of the prime (i.e. brain injury) disturbance that has to be also attenuated when muscle weakness is attenuated/reversed (prime lesion↔secondary lesion). Thereby, the multitude of relations might be illustrative. Along with counteracted muscle weakness counteracted was a vascular failure ^{[19][37][59][66][67][68][69][70][71][72][73][74]}[51,52,53,54,56,57,67,80,81,82,83,84]. Evidently, BPC 157 therapy substantiated the consistently preserved and recovered muscle function in all these experiments. These were the preserved Morris water maze test, the inclined-beam-walking test, the lateral push test (stroke rats) ^[75][68], the righting reflex (concussed mice) test ^[76][146], the counteracted ataxia and impaired forelimb function (cuprizone-induced multiple sclerosis-like rats) test ^[77][149], and the test to regain tail function after tail paralysis (spinal cord compression) ^[78][79][147,148]. This may be the translation to preserve muscle function that might consistently occur as a well-functioning cytoprotection loop (i.e., brain–periphery) as a part of the realized brain–gut axis central–peripheral functioning on both sides (for review see, i.e., ^[1][2][6][7][1,2,6,7]). To this point, the equal counteraction of various brain and spinal cord lesions may be illustrative. Those counteracted were both early and delayed neural hippocampal damages (stroke rats) ^[75][68]; brain lesions (concussed mice) ^[76][146]; lesions in various brain areas, with the most prominent damages in the corpus callosum, laterodorsal thalamus, nucleus reunions, and anterior horn motor neurons (cuprizone-induced multiple sclerosis-like rats) ^[77][149]; and markedly attenuated spinal cord compression hematoma and lesions (spinal cord compression) ^[78][79][147,148]. Within the same dosage range, there was a similar counteraction of myocardial infarction and myocardial reinfarction, along with brain injury mitigation and the counteraction of severe vascular and multiorgan failure (activated azygos vein direct blood flow delivery) ^{[19][37][59][66][67][68][69][70][71][72][73][74]}[51,52,53,54,56,57,67,80,81,82,83,84]. In the intoxicated rats overdosed with lithium, severe myocardial brain lesions and muscular weaknesses were timely correlated, and they were consistently counteracted by the therapy ^[59][56]. Thus, these combined findings illustrated that, with BPC 157 therapy, a well-functioning cytoprotection loop (brain–periphery) largely occurred ^[5][9][5,9]. Many smooth muscles appeared as a particular target of BPC 157 therapy. The beneficial effect occurred on many sphincters during the conditions of sickness. The recovery of the sphincters’ distinctive functions (lower esophageal sphincter, pyloric sphincter ^{[28][40][80][81][82][83][84][85][86][87]}[46,95,106,162,163,164,165,166,167,168], pupil ^[88][89][169,170], urinary sphincter ^[90][91][92][48,171,172]) suggests that BPC 157 therapy might exert a distinctive effect. This effect may be dependent on the given lesion and condition, the maintained normal function, or the recovery of the disturbed function. This may preserve normal functioning anti-reflux effects (increases lower esophageal sphincter pressure, decreases pyloric sphincter pressure ^[81][162]) or maintain normal pupil diameter ^[88][169] or normal leak point pressures ^[91][171]. Recovery of sphincter failure occurred against a variety of agents and procedures. These included absolute alcohol ^[28][40][95,106], NSAIDs and/or neuroleptics and/or NO agents ^[80][86][46,167], tube insertions into sphincters ^[81][82][83][162,163,164], acute pancreatitis (bile duct ligation) ^[83][164], creation of fistulas ^[85][92][93][58,166,172], and the particular creation of anastomoses ^[87][168] (the lower esophageal sphincter, pyloric sphincter). Atropine ^[88][169], NO agents, L-NAME and/or L-arginine ^[88][169], and glaucoma (episcleral veins cauterization) ^[89][170] induced pupil dysfunction. Transabdominal urethrolysis, prolonged vaginal dilatation ^[91][171], and cyclophosphamide caused urinary sphincter dysfunction ^[90][48]. Those counteracted were different (even opposite) dysfunctions, i.e., NOS blockades, NOS over-activities, mioses, and mydriases ^[40][80][88][46,106,169]. Thus, with BPC 157 therapy, the maintenance or recovery of the function of the sphincter is operative against different peripheral and/or central insults (i.e., esophagitis ^{[28][40][80][81][82][83][85][86][93]}[46,58,95,106,162,163,164,166,167], glaucoma ^[88][89][169,170], stress urinary incontinence ^[91][171], and cytostatic-induced bladder dysfunction ^[90][48]).

4. Brain Injury Concomitant Pathology

The more and more extensive range of beneficial effects should be simultaneously present in both the periphery and central nervous system to give rise to the brain–gut and gut–brain axes’ function as a verified therapeutic effect. Despite the particular mechanism, the resolving key highlighted the concept of cytoprotection. Illustratively, as defined within prostaglandin in the stomach and other tissues ^[94][13], with the general prostaglandin system significance, these arguments were provided with the counteraction of the noxious course following NSAIDs ^[95][34] by BPC 157 therapy. These were non-specific NSAIDs ^{[18][96][97][98][99][100][101][102]}[36,37,38,40,41,42,43,44] as well as specific NSAIDs ^[103][39]. There were simultaneous counteractions of both central and peripheral injuries ^{[96][97][98][99][103]}[36,37,38,39,40]. To analyze the obtained large range of the therapeutic effects of BPC 157, several particular points in NSAIDs-induced lesions (paracetamol, diclofenac, ibuprofen, and celecoxib) should be highlighted ^{[18][96][97][98][99][100][101][102][103]}[36,37,38,39,40,41,42,43,44] with the application of overdosed NSAID regimens. For example, centrally, the particular aspect of the sudden onset of encephalopathy with severe seizures (paracetamol) or prolonged sedation and/or unconsciousness (diclofenac, ibuprofen) might have been indicative; the worst lesions were in the cerebellum and more in the white matter (paracetamol) or in the cerebral cortex and cerebellar nuclei in the Purkinje cells (diclofenac, ibuprofen, and celecoxib). Peripherally, huge liver lesions (paracetamol) or gastrointestinal and liver lesions (diclofenac, ibuprofen (hepatomegaly), and celecoxib) occurred. Therefore, it might have been that the recovery of the essential cytoprotective prostaglandin system, which was supposed to be inhibited with NSAIDs, occurred as the key to reestablishing brain–gut axis function. The effective, therapeutic μg-ng range of BPC 157, simultaneously occurring peripherally and centrally, might have been illustrative ^{[18][96][97][98][99][100][101][102][103]}[36,37,38,39,40,41,42,43,44]. Indicatively, these lesions and their worsening effects were related to the NO system. In short bowel rats (i.e. massive intestinal resection-, massive intestinal resection-plus-diclofenac-, and massive intestinal resection-plus-diclofenac-plus-L-NAME-treated (cyclooxygenase (COX)–NO system inhibition ^[99][40]), it was evident that the application of the NOS blocker L-NAME ^[99][40] aggravated the harmful effects of the NSAIDs (i.e., poor anastomosis healing, failed intestine adaptation, and aggravated gastrointestinal, liver, and brain lesions in diclofenac short-bowel rats ^[99][40]). BPC 157 completely ameliorated symptoms in all these circumstances, thus, also successfully resolving cyclooxygenase (COX)–NO system inhibition ^[99][40]. Notably, scholars used the distinctive course of the stomach–liver–brain lesions after an overdose of insulin and equal antagonization by BPC 157 therapy to support the more general significance ^[104][35]. The characteristics were hypoglycemic seizures, eventually leading to death, which appeared 90 min after insulin, and the severe damage of neurons in the hippocampus and the cerebral cortex. Likewise, the characteristics were no fatal outcome, no hypoglycemic seizures, and markedly fewer damaged brain neurons in BPC 157-treated rats. The particular indications were higher blood glucose levels (glycogen was still present in hepatocytes) ^[104][35]. In the prominent calcification of liver blood vessels (both insulin pathways should be inhibited for the calcification ^[105][106][181,182]) in an insulin-administration period of a few hours, BPC 157 administration markedly attenuated ^[104][35], the liver appeared to be a normal weight, fatty liver was counteracted, and increased enzyme serum values were counteracted. BPC 157-treated specimens had only occasional small gastric lesions ^[104][35]. Thus, BPC 157 recovered both insulin pathways (insulin and glucagon release are under KATP channel control as well as under the control of hypothalamus-brain stem hypoglycemia-induced vagal signaling ^[105][181]) during hypoglycemia and regained brain–gut function integrity. Thus, these findings might highlight the effective simultaneous recoveries of the brain–gut and gut–brain axes’ functioning with BPC 157 therapy applications. As mentioned before, the advantages of this therapy, including the recovery of the essential bodily system involved, were summarized in the NSAIDs, short-bowel surgery, and insulin brain injury studies ^{[18][96][97][98][99][100][101][102][103]}[36,37,38,39,40,41,42,43,44]. As a major advantage to verify additional considerable general significance, there was the counteracted leaky gut syndrome in the rats does with indomethacin and the recovery of all of the leaky-gut-syndrome-deranged molecular pathways ^[100][41].

5. Thrombosis

There was, commonly noted, marked thrombosis, both centrally and peripherally, during the occlusion/occlusion-like syndrome and progressing brain and internal organs’ lesions. There were intracerebral and interventricular bleedings and hemorrhages in the internal organs as well. Thus, such thromboses (and hemorrhages) might provide particular requirements for the function of the brain–gut and gut–brain axes ^{[19][37][59][66][67][68][72][73][74]}[51,52,53,56,57,81,82,83,84]. With BPC 157 therapy, the particular beneficial effect on the brain–gut axis and gut–brain function should instantly resolve a considerable number of the failed blood vessels, which might have been unable to be spontaneously activated upon injury in the recruitment of the collateral blood vessels. In resolving the harmful occlusion/occlusion-like syndrome in a way reliant on the given vascular injury, this therapy commonly occurred and might encompassed a large number of distinctive vessel pathways, both peripherally and centrally, as useful collaterals. Specifically, peripherally, there were many vessels involved that were identified. There were veins (the left ovarian ^[70][67], inferior mesenteric ^[69][54], inferior anterior pancreaticoduodenal, superior anterior pancreaticoduodenal, pyloric ^[67][68][52,53], and azygos ^{[19][37][59][71][72][73][74]}[56,57,80,81,82,83,84]) and arteries (the inferior mesenteric artery and inferior anterior pancreaticoduodenal ^[66][51]) depending on the injury, with occluded veins (i.e., inferior caval, superior mesenteric) or occluded arteries (superior mesenteric) as alternative rescuing venous or arterial pathways. Centrally, (para)sagittal venous collateral circulation occurred ^[72][81]. Thus, the Virchow triad consequences may have been resolved ^{[19][37][59][66][67][68][69][70][71][72]}[51,52,53,54,56,57,67,80,81,82]. As evidenced by deep vein thrombosis (inferior caval vein syndrome), consumption thrombocytopenia, given the decreased bleeding, timely carried out to the prolonged bleeding and increased thrombosis, was also counteracted by BPC 157 therapy ^[70][67]. The parallel counteractions of the corresponding lesions ^{[19][37][59][66][67][68][72][73][74]}[51,52,53,56,57,81,82,83,84] were essential to prove that these effects (i.e., BPC 157 attenuated the spontaneous bleeding ^{[18][37][40][101][107][108]}[42,43,82,106,183,184] and the prolonged bleeding after anti-coagulants ^[18][101][42,43]; anti-thrombotic agents ^[101][42]; and the NOS substrate L-arginine, alone or with amputation (tail, leg) ^[18][43] and organ perforation (stomach, cecum) ^[107][108][183,184]), occurred accordingly, while the coagulation pathways were not affected ^{[18][101][102]}[42,43,44]. The same combined effect occurred with concussive brain injuries ^[76][146]. In addition, there was a recovery after the spinal cord compression ^[78][79][147,148]. Furthermore, aggregometry and thromboelastometry studies showed that BPC 157 given with aspirin, clopidogrel, or cilostazol in rats might specifically maintain the function of thrombocytes (i.e., counteracted inhibition on aggregation activated by arachidonic acid, ADP, collagen, and arachidonic acid/PGE1) ^[102][44]. Of note, this particular combining effect (counteracted thrombosis, counteracted hemorrhage, both peripherally and centrally) may also be conceptually resolved within the BPC 157 cytoprotection/organoprotection effect (assuming the simultaneous healing of different tissues ^{[1][2][7][27]}[1,2,7,85]) combined with wound healing (i.e., implied direct cell protection against direct injury and simultaneous healing ^[8][109][8,73]). There was, in a particular way, resolved wounding (i.e., myotendinous junction recovery, resolved brain and internal organs lesions), as evidenced by the BPC 157 effects in particular ^{[1][2][7][8][109]}[1,2,7,8,73]. Furthermore, wound/cytoprotection terms (i.e., innate endothelium maintenance) might illustrate particularities that might equally resolve both bleeding and thrombosis. Illustrative equations are resolved consequences of the abdominal aorta anastomosis ^[110][185] and amputation of the leg or tail ^[18][101][42,43]. Early BPC 157 therapy counteracted the formation of obstructing thrombi. Likewise, the delayed application rapidly annihilated the fully established obstructing thrombi ^[110][185], and post-amputation bleeding was decreased ^[18][101][42,43].  Finally, in addition to the particular maintenance of the thrombocytes’ function ^[102][44], an illustrative practical aspect might have been both the prevention of leg disability and rapidly reestablishing leg function ^[110][185] that should be mentioned in rats after the creation of abdominal aorta anastomoses ^[110][185] in parallel with the counteracting effect on obstructing thrombi ^[110][185]. Such a demonstration ^[110][185] is in keeping with the findings in the stroke rats, considering counteracted brain lesions and fully recovered function ^[75][68].