Is there an optimal age for recovery from motor cortex lesions? I. Behavioral and anatomical sequelae of bilateral motor cortex lesions in rats on postnatal days 1, 10, and in adulthood.

Department of Psychology and Neuroscience, University of Lethbridge, AB T1K 3M4, Lethbridge, Canada.
Brain Research (Impact Factor: 2.84). 12/2000; 882(1-2):62-74.
Source: PubMed


Rats were given bilateral lesions of the motor cortex on the day of birth (P1), tenth day of life (P10), or in adulthood. They were trained on several motor tasks (skilled forelimb reaching, beam traversing, tongue extension), general motor activity, and a test of spatial learning (Morris water task). Although all lesion groups were impaired at skilled reaching, the P10 group was less impaired than either of the other two lesion groups. Furthermore, on the other motor tests the P10 group did not differ from controls whereas both P1 and adult groups were impaired. Only the P1 lesion group was impaired at the acquisition of the Morris water task. Anatomical analyses revealed that the P1 and P10 rats had smaller brains than the other two groups as well as having a generalized decrease in cortical thickness. Dendritic analysis of layer III pyramidal cells in the parietal cortex revealed a decrease in apical arbor in the lesion groups and an increase in the basilar arbor of the P1 and adult lesion animals. The P1 and adult operated groups showed an increase in spine density in the basilar dendrites of layer V pyramidal cells. Finally, analysis of the pattern of corticospinal projections revealed that the P1 animals had a markedly wider field of corticospinal projection neurons than any of the other groups. The widespread anatomical changes in all lesion groups versus the relatively better behavioral recovery after P10 lesions suggests that day 10 represents an optimal period for adapting to brain damage and subsequent brain reorganization.

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    • "The long-standing Kennard Principle states that lesions in infancy are associated with more complete recovery than in adults (Dennis, 2010). More recent work, however , has found that a subset of early insults may be especially devastating (Kolb et al., 2000) because, in addition to the injury, there is a longer-term derailment of developmental programs, due in part to the consequence of critical-period plasticity. Additional work is required to fully elucidate time windows and factors that balance the potential for increased recovery with the increased vulnerability of the immature brain (Anderson et al., 2011). "
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    • "Kolb and colleagues describe qualitatively different changes in distribution of synapses in young and old animals housed in complex environments and those provided with tactile stimulation, with these morphological responses paralleled by behavioural enhancement (Kolb and Gibb, 2001). Benefits were more robust for animals injured earlier (which were more severely impaired) than those injured later (which had better spontaneous recovery) (Kolb et al., 2000a). Timing of environmental manipulation post-injury is critical, with little impact acutely, but better recovery associated with exposure to an enriched environment after the acute recovery period (Giza et al., 2005). "
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    • "In particular, the therapeutic properties of A2AR antagonists may arise from their ability to produce a brain state with greater potential to respond to insult, a state similar to the early neonatal period. In studies comparing the effects of brain injury at PND 1, PND 10 and in adults, optimal recovery occurs from lesions produced at PND 10 (Kolb et al., 2000; Gonzalez et al., 2003). This timeline for optimal reorganization parallels the developmental pattern of IEG expression in the current study. "
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