Effects of pituitary adenylate cyclase activating polypeptide in a rat model of traumatic brain injury.
Pituitary adenylate cyclase activating polypeptide (PACAP) is a widely distributed neuropeptide that has numerous different actions. Recent studies have shown that PACAP exerts neuroprotective effects not only in vitro but also in vivo, in animal models of global and focal cerebral ischemia, Parkinson's disease and axonal injuries. Traumatic brain injury has an increasing mortality and morbidity and it evokes diffuse axonal injury which further contributes to its damaging effects. The aim of the present study was to examine the possible neuroprotective effect of PACAP in a rat model of diffuse axonal injury induced by impact acceleration. Axonal damage was assessed by immunohistochemistry using an antiserum against beta-amyloid precursor protein, a marker of altered axoplasmic transport considered as key feature in axonal injury. In these experiments, we have established the dose response curves for PACAP administration in traumatic axonal injury, demonstrating that a single post-injury intracerebroventricular injection of 100 microg PACAP significantly reduced the density of damaged, beta-amyloid precursor protein-immunoreactive axons in the corticospinal tract.
Farkas
Orsolya
O
Department of Neurosurgery, University of Pécs, Medical Faculty, Hungary.
Tamás
Andrea
A
Zsombok
Andrea
A
Reglodi
Dóra
D
Pál
József
J
Büki
Andras
A
Lengvári
István
I
Povlishock
John T
JT
Dóczi
Tamás
T
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects; D001369:Axons / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D009414:Nerve Growth Factors / Q000008:administration & dosage / Q000627:therapeutic use*; D009479:Neuropeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051381:Rats; D017208:Rats, Wistar
C495403:Adcyap1 protein, rat; D016564:Amyloid beta-Protein Precursor; D009414:Nerve Growth Factors; D009479:Neuropeptides; D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide