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Db-cAMP applied to the Red Nucleus in rat improves the regenerative response of the rubrospinal tract after cervical spinal cord injury

University of British Columbia

A high cervical injury to the rubrospinal tract (RST) generally results in cellular and nuclear atrophy of the rubral neurons, abortive axonal regeneration and eventual retraction from the forming injurious scar and enlarging cavity. The neuronal cell body response to axonal injury plays an important role in the failure of central nervous system (CNS) neurons to regenerate. Adult mammalian CNS neurons fail to re-express a variety of genes and signalling factors, such as cAMP, after axotomy that are seen at increased levels in regenerating peripheral neurons or in developing CNS neurons. By mimicking the sustained increase in cAMP levels, prior to or during an upper cervical (C3/4) crush injury of the dorsolateral funiculus in adult male Sprague-Dawley rats using the membrane permeant analogue dibutyryl cAMP (db-cAMP) near the vicinity of rubrospinal neurons, will enhance the regenerative cell body response in order to promote axonal sprouting or regeneration to and across the site of a spinal cord injury. Two experimental groups, acute and pre-treatment, were used. Both groups received either 25mM db-cAMP (treatment) or vehicle (control) solutions delivered via 14 day mini osmotic-pumps. The pretreated group had db-cAMP infused beginning one week prior to injury for two weeks while the acutely treated group received concurrent treatment with injury. The rubrospinal tract was anterogradedly traced with biotinylated dextran amine (BDA) for quantification purposes. Camera lucida like reconstructions (CLLRs) were created for enhanced visualization and density calculation of the RST. Changes in behaviour were assessed using the vertical exploration test. Application of db-cAMP to the RN in both the acute and pretreated groups increased the number of labelled rubrospinal fibres in the gray matter and proximal to the site of injury in comparison to the controls. Db-cAMP treatment did not reduce lesion sizes nor were there any visibly traced fibres caudal to the site of injury in any of the treatment groups. Unexpectedly, pre-treatment of db-cAMP conferred no advantages over acute treatment. Behavioural analysis of spontaneous forelimb usage as indicated by the vertical exploration test revealed no significant differences between any of the db-cAMP and control groups.

Text

2012-10-15

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/43395

Neuroscience

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/