Neuroprotektivni učinak egzogenog pentadekapeptida BPC 157 pri eksperimentalnoj kraniocerebralnoj ozljedi

Tudor, Mario (2010) Neuroprotektivni učinak egzogenog pentadekapeptida BPC 157 pri eksperimentalnoj kraniocerebralnoj ozljedi. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, an antiulcer peptide in inflammatory bowel disease trials (PL 14736), no toxicity reported) was shown to improve muscle crush injury. Now, after drop weight gradually induced traumatic brain injury (TBI) in mice, BPC 157 regimens (10.0 µg, 10.0 ng/kg i.p.) showed marked attenuation and improved early outcome, and then minimal postponed mortality throughout 24 h post-injury, and eventually, attenuated traumatic lesion’s intensity (subarachnoidal and intraventricular hemorrhage, brain laceration, hemorrhagic laceration), consecutive brain edema considerably improved. The improved conscious/unconscious/death ratio in TBI-mice was commonly seen after TBI produced with force impulse of the 0.068 Ns, 0.093 Ns, 0.113 Ns, 0.130 Ns, 0.145 Ns, and 0.159 Ns. Counteraction (less unconsciousness, lesser mortality) with both µg- and ng-regimens included force impulse 0.068-0.145 Ns; maximal TBI-severity (force impulse 0.159 Ns) presented µg-regimen effectiveness only. Furthermore, to determine time-relation between the medication time and the onset of the beneficial effects, we showed that even one BPC 157 application immediately before injury was beneficial in mice subjected to force impulse of 0.093 Ns-TBI. For stronger TBIs (force impulse 0.130 Ns, 0.145 Ns, 0159 Ns), the time relation to improve conscious/unconscious/death ratio was: 5 min (0.130 Ns-TBI), 20 min (0.145 Ns-TBI) or 30 min (0.159 Ns-TBI).

Abstract in Croatian

Pokazano je da antiulkusni peptid, želučani pentadekapeptid BPC 157 (GEPPPGKPADDAGLV, u pokusima pri upalnim bolestima crijeva (PL 14736), bez toksičnosti), poboljšava cijeljenje zgnječenog mišićnog tkiva. Kod stupnjevito rastuće traumatske ozljede mozga (TBI) nanesene padajućim utegom u miša doze BPC 157 (10.0 µg, 10.0 ng/kg i. p.) pokazale su znatno smanjenje i poboljšanje ranog posljedka i tek minimalnu naknadnu smrtnost kroz 24-satni period nakon ozljede te konačno smanjenje jačine traumatske ozljede (subarahnoidalna i intraventrikularna hemoragija, laceracija mozga, hemoragička laceracija), znatno poboljšanje konsekutivnog edema mozga. Poboljšani omjer budni/komatozni/uginuli u miševa s TBI najčešće je uočen pri TBI nanesenom impulsom sile od 0.068 Ns, 0.093 Ns, 0.113 Ns, 0.130 Ns, 0.145 Ns, i 0.159 Ns. Suprotni učinak (više budnih, manje uginulih) kako s µg- tako i s ng-dozama viđen je pri primjeni impulsa sile od 0.068-0.145 Ns; maksimalnom težinom TBI (impuls sile od 0.159 Ns) samo pri µg - dozama. Da bi se odredio odnos vremena između primjene medikacije i pojave povoljnih učinaka primijenjenih tvari, dokazali smo da je primjena čak i samo jedne doze BPC 157 neposredno pred nanošenje ozljede djelovala povoljno u miša izloženog impulsu sile od 0.093 Ns-TBI. Za teže TBI (impuls sile 0.130 Ns, 0.145 Ns, 0159 Ns), protok vremena potreban za poboljšanje omjera budni/komatozni/uginuli iznosio je: 5 min (0.130 Ns-TBI), 20 min (0.145 Ns-TBI) ili 30 min (0.159 Ns-TBI).

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