Acetylcholinesterase Inhibition and Locomotor Function after Motor-Sensory Cortex Impact Injury
Autor: | Margareth Roch, Yumei Guo, Keith M. Norman, Daniel P. Holschneider, Oscar U. Scremin |
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Rok vydání: | 2011 |
Předmět: |
Male
Physostigmine Traumatic brain injury Motor Activity Rats Sprague-Dawley chemistry.chemical_compound Cortex (anatomy) medicine Animals Sensory cortex Balance (ability) Motor Cortex Recovery of Function Somatosensory Cortex medicine.disease Gait Acetylcholinesterase Rats medicine.anatomical_structure chemistry Brain Injuries Rotarod Performance Test Anesthesia Cholinergic Cholinesterase Inhibitors Neurology (clinical) Psychology Neuroscience Locomotion medicine.drug |
Zdroj: | Journal of Neurotrauma. 28:1909-1919 |
ISSN: | 1557-9042 0897-7151 |
DOI: | 10.1089/neu.2011.1978 |
Popis: | Traumatic brain injury (TBI) induces transient or persistent dysfunction of gait and balance. Enhancement of cholinergic transmission has been reported to accelerate recovery of cognitive function after TBI, but the effects of this intervention on locomotor activity remain largely unexplored. The hypothesis that enhancement of cholinergic function by inhibition of acetylcholinesterase (AChE) improves locomotion following TBI was tested in Sprague-Dawley male rats after a unilateral controlled cortical impact (CCI) injury of the motor-sensory cortex. Locomotion was tested by time to fall on the constant speed and accelerating Rotarod, placement errors and time to cross while walking through a horizontal ladder, activity monitoring in the home cages, and rearing behavior. Assessments were performed the 1st and 2nd day and the 1st, 2nd, and 3rd week after TBI. The AChE inhibitor physostigmine hemisulfate (PHY) was administered continuously via osmotic minipumps implanted subcutaneously at the rates of 1.6-12.8 μmol/kg/day. All measures of locomotion were impaired by TBI and recovered to initial levels between 1 and 3 weeks post-TBI, with the exception of the maximum speed achievable on the accelerating Rotarod, as well as rearing in the open field. PHY improved performance in the accelerating Rotarod at 1.6 and 3.2 μmol/kg/day (AChE activity 95 and 78% of control, respectively), however, higher doses induced progressive deterioration. No effect or worsening of outcomes was observed at all PHY doses for home cage activity, rearing, and horizontal ladder walking. Potential benefits of cholinesterase inhibition on locomotor function have to be weighed against the evidence of the narrow range of useful doses. |
Databáze: | OpenAIRE |
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