A critical maturational period of reduced brain vulnerability to injury. Astudy of cerebral glucose metabolism in cats

We have developed a feline cerebral hemispherectomy model as an analog to t he surgical procedure used in pediatric intractable epilepsy. Previous work with this model has shown a remarkable plasticity associated with an early period of brain development, which we have defined using morphological, ce rebral metabolic and behavioral methods. However, the important functional- metabolic bracketing of this period has not yet been performed. We have con ducted the present study to answer questions raised by our previous finding s using [C-14] 2-deoxy-D-glucose autoradiography but only including animals lesioned at day 10 postnatally (P10) or in adulthood. The questions were; (a) is there any age better than P10 for an optimal metabolic outcome?, and (b) can we determine a cutoff point for the beneficial effects of the youn g age-at-lesion? Twenty-one adult cats were studied. Seven cats served as i ntact controls, five received a left hemineodecortication at P30, three at P60, three at P90 and three at P120, respectively. Histological analysis in dicated that the extent of the lesion was similar between the age groups. L ocal glucose metabolic rates (LCMRglc) were measured in 50 structures bilat erally and used to calculate overall LCMRglc for seven grouped sites within the cerebral cortex, thalamus, basal ganglia, mesencephalic tegmentum. (an d tectum), limbic system and cerebellum. Results indicated a widespread bil ateral depression of LCMRglc in all age-at-lesion groups. The depression in overall LCMRglc across all structures measured in each hemisphere was sign ificant (P <0.05) for the P120 group relative to intacts for both ipsilater al (left) and contralateral (right) sides of the brain. The ipsilateral tha lamus was the region most effected by the injury, with significant losses f or all age-at-lesion groups. In addition, while there were widespread depre ssions for all lesion groups, these losses were significant for the P120 gr oup in five groups of structures ipsilaterally (thalamus, basal ganglia, te ctum, limbic system, cerebellum) and in three contralaterally (thalamus, te ctum, cerebellum). In contrast, significant depressions for the earlier age -at-lesion groups (P30, P60, P90) were found only in the ipsilateral thalam us and bilaterally in the tectum. These results, together with our previous results for the P10 group, indicate a relative sparing of LCMRglc after he mineodecortication during the first 60 days of life, with gradually decreas ing plasticity thereafter, such that there is some residual sparing at 90 d ays of age, and afterwards an almost complete loss of metabolic plasticity, with lesions at P120 producing a dismal outcome. These results complement earlier morphological and behavioral studies and support the concept of a ' Critical Maturational Period' of reduced vulnerability to developmental inj ury. (C) 2001 Elsevier Science B.V. All rights reserved.