title: A critical maturational period of reduced brain vulnerability to injury. A study of cerebral glucose metabolism in cats.
abstract: We have developed a feline cerebral hemispherectomy model as an analog to the 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, cerebral metabolic and behavioral methods. However, the important functional-metabolic bracketing of this period has not yet been performed. We have conducted the present study to answer questions raised by our previous findings using [14C] 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 young age-at-lesion? Twenty-one adult cats were studied. Seven cats served as intact controls, five received a left hemineodecortication at P30, three at P60, three at P90 and three at P120, respectively. Histological analysis indicated that the extent of the lesion was similar between the age groups. Local glucose metabolic rates (LCMR(glc)) were measured in 50 structures bilaterally and used to calculate overall LCMR(glc) for seven grouped sites within the cerebral cortex, thalamus, basal ganglia, mesencephalic tegmentum (and tectum), limbic system and cerebellum. Results indicated a widespread bilateral depression of LCMR(glc) in all age-at-lesion groups. The depression in overall LCMR(glc) across all structures measured in each hemisphere was significant (P<0.05) for the P120 group relative to intacts for both ipsilateral (left) and contralateral (right) sides of the brain. The ipsilateral thalamus was the region most effected by the injury, with significant losses for all age-at-lesion groups. In addition, while there were widespread depressions for all lesion groups, these losses were significant for the P120 group in five groups of structures ipsilaterally (thalamus, basal ganglia, tectum, limbic system, cerebellum) and in three contralaterally (thalamus, tectum, cerebellum). In contrast, significant depressions for the earlier age-at-lesion groups (P30, P60, P90) were found only in the ipsilateral thalamus and bilaterally in the tectum. These results, together with our previous results for the P10 group, indicate a relative sparing of LCMR(glc) after hemineodecortication during the first 60 days of life, with gradually decreasing plasticity thereafter, such that there is some residual sparing at 90 days 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 injury.
authors.affiliation: Department of Neuroscience, New York College of Osteopathic Medicine, PO Box 8000, Old Westbury, NY 11568-8000, USA.
authors.forename: T D
authors.initials: TD
authors.lastname: Schmanke
authors.forename: J R
authors.initials: JR
authors.lastname: Villablanca
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000493:pharmacokinetics; D001479:Basal Ganglia / Q000254:growth & development / Q000378:metabolism; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D001933:Brain Stem / Q000254:growth & development / Q000378:metabolism; D002415:Cats; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism; D002541:Cerebral Decortication; D003423:Critical Period, Psychological; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004827:Epilepsy / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D008032:Limbic System / Q000254:growth & development / Q000378:metabolism; D019579:Neocortex / Q000254:growth & development / Q000378:metabolism; D009473:Neuronal Plasticity; D013788:Thalamus / Q000254:growth & development / Q000378:metabolism
chemical_list: D000963:Antimetabolites; D003847:Deoxyglucose; D005947:Glucose