Developmental neuroplasticity in a model of cerebral hemispherectomy and stroke

Cerebral hemispherectomy, a last resort treatment for childhood epilepsy, is a standard procedure which dramatically illustrates the resilience of the brain to extensive damage. If this operation, also mimicking long-term, extensive unilateral capsular stroke, is performed in postnatal cats of up to 60 days of age, there is a remarkable recovery/sparing of neurological functions that is not seen when the lesion occurs during late fetal life or in adulthood. A long-term effect at all ages is loss of neurons in bilateral brain areas remote from the resection site. This is pronounced in adult cats and shows intriguing, paradoxical features in fetal animals, but is substantially attenuated in neonatal cats. Similarly, large-scale reinnervation of subcortical sites (sprouting) by neurons of the remaining, intact hemisphere is prominent in young cats, but not in fetal or adult animals. These and other restorative processes (described herein) in young postnatal animals are matched by relatively higher rates of local cerebral glucose utilization, supporting the notion that they underlie the improved behavioral outcome. Thus, during a critical, defined stage of maturation, presumably common to higher mammals including humans, the brain entirely remodels itself in response to extensive but focal injury. Perhaps the molecular environment allowing for rescue of neurons and enhanced reinnervation at a specific developmental stage could be recreated in subjects with brain lesions at less favorable ages, thereby helping to restore circuitry and spare neurons. However, replacement via transplantation of neurons eliminated by the damage appears to be crucial in attempts to further preserve cells located remotely but yet destined to die or decrease in size. This article presents abundant evidence to show that there is a surprisingly comprehensive long-term morphological remodeling of the entire brain after extensive unilateral damage and that this occurs preferentially during a discrete period of early life. Additional evidence strongly suggests that the remodeling underlies the outstanding behavioral and functional recovery/sparing following early cerebral hemispherectomy. We argue that this period of reduced brain vulnerability to injury also exists in other higher mammals, including man, and suggest ways to enhance restorative processes after stroke/hemispherectomy occurring at other ages.