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Neurorehabil Neural Repair. 2013 Nov-Dec;27(9):889-99. doi: 10.1177/1545968313491003. Epub 2013 Jun 18.

Beneficial effects of minocycline and botulinum toxin-induced constraint physical therapy following experimental traumatic brain injury.

Author information

1
1San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA.

Abstract

BACKGROUND:

Effective recovery from functional impairments caused by traumatic brain injury (TBI) requires appropriate rehabilitation therapy. Multiple pathways are involved in secondary injury and recovery suggesting a role for multimodal approaches.

OBJECTIVE:

Here, we examined the efficacy of the anti-inflammatory agent minocycline and botulinum toxin (botox)-induced limb constraint with structured physical therapy, delivered alone or in combination, after a severe TBI produced by a controlled cortical impact in rats.

METHODS:

Minocycline was administered at 25 mg/kg daily for 2 weeks beginning 1 day after TBI or sham surgery. For constraint/physical therapy, botox-type A was injected into the nonaffected forearm muscle 1 day after injury and 2 weeks of physical therapy commenced at 5 days after injury. Functional evaluations were conducted 8 weeks after injury.

RESULTS:

Minocycline, either as a monotherapy or as combination treatment with botox/physical therapy significantly reduced impairments of spatial learning and memory in the water maze test, whereas botox/physical therapy reduced forelimb motor asymmetry and improved manual dexterity in the cylinder and vermicelli handling tests, A synergistic effect between the 2 treatments was observed when rats performed tasks requiring dexterity. Inflammation was attenuated in the peri-contusion cortex and hippocampus in all TBI groups receiving mono or combination therapies, though there was no significant difference in lesion size among groups.

CONCLUSION:

These data provide a rationale for incorporating anti-inflammatory treatment during rehabilitation therapy.

KEYWORDS:

botox; constraint-induced movement therapy (CIMT); controlled cortical impact; glial fibrillary acidic protein (GFAP); microglia; rehabilitation

PMID:
23778701
DOI:
10.1177/1545968313491003
[Indexed for MEDLINE]

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