Posttraumatic Administration of Pituitary Adenylate Cyclase Activating Polypeptide in Central Fluid Percussion Injury in Rats

Kövesdi, Erzsébet and Tamás, Andrea and Reglődi, Dóra and Farkas, Orsolya and Pál, József and Tóth, Gábor and Bukovics, Péter and Dóczi, Tamás and Büki, András (2008) Posttraumatic Administration of Pituitary Adenylate Cyclase Activating Polypeptide in Central Fluid Percussion Injury in Rats. Neurotoxicity Research, 13 (2). pp. 71-78. ISSN 1029-8428

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Abstract

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 μg PACAP was administered intracerebroventricularly. DAI was assessed by immunohistochemical detection of β-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 vehicletreated 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.

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