Unilateral injury to the forelimb representation area of the sensorimotor cortex (FL-SMC) in adult rats causes over-reliance on the unimpaired forelimb for postural-motor movements, as well as overgrowth of layer V pyramidal cell dendrites in the homotopic cortex of the noninjured hemisphere. The overgrowth appears to be use-dependent because it can be prevented by restricting movements of the unimpaired forelimb. Additionally, restricting the unimpaired forelimb in animals with FL-SMC damage results in significantly greater behavioral dysfunction when examined 2 d after cast removal (compared to that after impaired-limb immobilization, or no limb immobilization). In the present study, the long-term behavioral and anatomical effects of limb immobilization were examined. Animals with FL-SMC lesions were fitted with casts immediately after the lesion that immobilized the impaired forelimb, the unimpaired forelimb, or neither forelimb for 15 d. Immobilization of the nonimpaired forelimb resulted in chronic prevention of dendritic growth and severe and chronic behavioral deficits. In addition, immobilization of the nonimpaired forelimb resulted in a dramatic exaggeration of the neuronal injury, presumably attributable to forced overuse of the impaired limb. Immobilization of the impaired forelimb resulted in no detectable neural changes and in only slightly increased and longer-lasting behavioral asymmetries (compared to nonimmobilized, lesioned animals), presumably attributable to mild disuse of the impaired limb. Immobilization of a single forelimb in nonlesioned rats resulted in no significant behavioral or anatomical changes. Together, these results suggest that although behavioral experience can enhance neural growth after brain injury, the region surrounding the injury may be vulnerable to behavioral pressure during the early postlesion period.

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Proliferation decreases in the neurogenic subventricular zone (SVZ) of mice after aspiration lesions of the cerebral cortex. We hypothesized that microglial activation may contribute to this given microglial activation attenuates neurogenesis in the hippocampus. Using CD45, CD11b, IB4, and IL-6 immunohistochemistry (IHC), BrdU IHC, and fluorescent bead tracking of peripheral monocytes into the brain, we compared microglial activation in the SVZ to non-neurogenic forebrain regions. SVZ microglia exhibited greater constitutive activation and proliferation than did microglia in non-neurogenic regions. In contrast to the SVZ, the dentate gyrus (DG) contained relatively few CD45(+) cells. After aspiration cerebral cortex lesions, microglia became activated in the cerebral cortex, corpus callosum, and striatum. SVZ microglial activation did not increase, and similarly, microglia in the DG were less activated after injury than in adjacent non-neurogenic regions. We next showed that SVZ microglia are not categorically refractory to activation, since deep cortical contusion injuries increased SVZ microglial activation. Macrophages migrate into the brain during development, but it is unclear if this is recapitulated after injury. Infiltration of microbead-labeled macrophages into the brain did not change after injury, but resident SVZ microglia were induced to migrate toward the injury. Our data show that both constitutive and postlesion levels of microglial activation differ between neurogenic and non-neurogenic regions.

Injection of an adenoviral (Ad) vector encoding human glial intrastriatal injection of 6-OHDA on the same side as the cell line-derived neurotrophic factor (GDNF) protects dopavector injection. AdGDNF injection into either the striatum minergic (DA) neurons in the substantia nigra (SN) of or SN significantly reduced the loss of FG labelled DA neuyoung rats. As Parkinson's disease occurs primarily in rons 5 weeks after lesion (P р 0.05). However, only striatal aged populations, we examined whether chronic biosyninjections of AdGDNF protected against the development thesis of GDNF, achieved by adenovirus-mediated delivery of behavioral deficits characteristic of unilateral DA of a GDNF gene (AdGDNF), can protect DA neurons and depletion. Striatal AdGDNF injections also reduced tyroimprove DA-dependent behavioral function in aged (20 sine hydroxylase fiber loss and increased amphetaminemonths) rats with progressive 6-OHDA lesions of the nigroinduced striatal Fos expression. These results demonstrate striatal projection. Furthermore, the differential effects of that increased levels of striatal, but not nigral, GDNF injecting AdGDNF either near DA cell bodies in the SN or biosynthesis prevents DA neuronal loss and protects DA at DA terminals in the striatum were compared. AdGDNF terminals from 6-OHDA-induced damage, thereby or control vector was injected unilaterally into either the strimaintaining DA function in the aged rat. atum or SN. One week later, rats received a unilateral

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Compensatory neural plasticity occurs in both hemispheres following unilateral cortical damage incurred by seizures, stroke, and focal lesions. Plasticity is thought to play a role in recovery of function, and is important for the utility of rehabilitation strategies. Such effects have not been well described in models of traumatic brain injury (TBI). We examined changes in immunoreactivity for neural structural and plasticity-relevant proteins in the area surrounding a controlled cortical impact (CCI) to the forelimb sensorimotor cortex (FL-SMC), and in the contralateral homotopic cortex over time (3-28 days). CCI resulted in considerable motor deficits in the forelimb contralateral to injury, and increased reliance on the ipsilateral forelimb. The density of dendritic processes, visualized with immunostaining for microtubule-associated protein-2 (MAP-2), were bilaterally decreased at all time points. Synaptophysin (SYN) immunoreactivity increased transiently in the injured hemisphere, but this reflected an atypical labeling pattern, and it was unchanged in the contralateral hemisphere compared to uninjured controls. The lack of compensatory neuronal structural plasticity in the contralateral homotopic cortex, despite behavioral asymmetries, is in contrast to previous findings in stroke models. In the cortex surrounding the injury (but not the contralateral cortex), decreases in dendrites were accompanied by neurodegeneration, as indicated by Fluoro-Jade B (FJB) staining, and increased expression of the growth-inhibitory protein Nogo-A. These studies indicate that, following unilateral CCI, the cortex undergoes neuronal structural degradation in both hemispheres out to 28 days post-injury, which may be indicative of compromised compensatory plasticity. This is likely to be an important consideration in designing therapeutic strategies aimed at enhancing plasticity following TBI.