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Posttraumatic administration of pituitary adenylate cyclase activating polypeptide in central fluid percussion injury in rats

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Abstract

Severalin vitro andin 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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Abbreviations

APP:

Amyloid precursor protein

CFP:

Central fluid percussion

CSpT:

Corticospinal tract

DAI:

Diffuse axonal injury; icv, intracerebroventricularly

MLF:

Medial longitudinal fascicle

PACAP:

Pituitary adenylate cyclase activating polypeptide

TBI:

Traumatic brain injury

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Authors and Affiliations

  1. Department of Neurosurgery, University of Pécs, Medical Faculty, Hungary

    Erzsébet Kóvesdi, József PáL, Péter Bukovics, Tamás Dóczi & András Büki

  2. Department of Anatomy, University of Pécs, Medical Faculty, Hungary

    Andrea Tamás & Dóra Reglodi

  3. Department of Radiology, University of Pécs, Medical Faculty, Hungary

    Orsolya Farkas

  4. Department of Medical Chemistry, University of Szeged, Hungary

    Gábor Tóth

  5. Clinical Neuroscience Research Group, Hungarian Academy of Sciences, Pécs, Hungary

    Péter Bukovics

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  1. Erzsébet Kóvesdi
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  2. Andrea Tamás
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  3. Dóra Reglodi
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  4. Orsolya Farkas
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  5. József PáL
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  6. Gábor Tóth
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  7. Péter Bukovics
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  9. András Büki
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Correspondence to András Büki.

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Kóvesdi, E., Tamás, A., Reglodi, D. et al. Posttraumatic administration of pituitary adenylate cyclase activating polypeptide in central fluid percussion injury in rats. neurotox res 13, 71–78 (2008). https://doi.org/10.1007/BF03033558

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