Posttraumatic administration of pituitary adenylate cyclase activating polypeptide in central fluid percussion injury in rats.
Several in vitro and in vivo experiments have demonstrated the neuroprotective effects of pituitary adenylate cyclase activating polypeptide (PACAP) in focal cerebral ischemia, Parkinson's disease and traumatic brain injury (TBI). The aim of the present study was to analyze the effect of PACAP administration on diffuse axonal injury (DAI), an important contributor to morbidity and mortality associated with TBI, in a central fluid percussion (CFP) model of TBI. Rats were subjected to moderate (2 Atm) CFP injury. Thirty min after injury, 100 microg PACAP was administered intracerebroventricularly. DAI was assessed by immunohistochemical detection of beta-amyloid precursor protein, indicating impaired axoplasmic transport, and RMO-14 antibody, representing foci of cytoskeletal alterations (neurofilament compaction), both considered classical markers of axonal damage. Analysis of damaged, immunoreactive axonal profiles revealed significant axonal protection in the PACAP-treated versus vehicle-treated animals in the corticospinal tract, as far as traumatically induced disturbance of axoplasmic transport and cytoskeletal alteration were considered. Similarly to our former observations in an impact acceleration model of diffuse TBI, the present study demonstrated that PACAP also inhibits DAI in the CFP injury model. The finding indicates that PACAP and derivates can be considered potential candidates for further experimental studies, or purportedly for clinical trials in the therapy of TBI.
Department of Neurosurgery, University of Pécs, Medical Faculty, Hungary.
Erzsébet
E
Kövesdi
Andrea
A
Tamás
Dóra
D
Reglodi
Orsolya
O
Farkas
József
J
Pál
Gábor
G
Tóth
Péter
P
Bukovics
Tamás
T
Dóczi
András
A
Büki
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D006133:Growth Substances / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D011712:Pyramidal Tracts / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar
D006133:Growth Substances; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide