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A critical maturational period of reduced brain vulnerability to developmental injury. I. Behavioral studies in cats
J R Villablanca1, P Carlson-Kuhta, T D Schmanke
1Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles 90024, USA. jvillablanca@mednet.ucla.edu
Insights
Brain injury in cats shows optimal recovery during a specific developmental window. This critical maturational period (CMP) suggests a universal principle for brain repair in mammals, including humans.
Area of Science:
- Neuroscience
- Developmental Biology
- Comparative Neurology
Background:
- Neocortical injury in early life can lead to varying degrees of behavioral deficits.
- Previous studies indicated better outcomes for fetal-compared to postnatal-lesioned cats.
- Understanding the timing of brain injury's impact is crucial for predicting recovery.
Purpose of the Study:
- To investigate the long-term behavioral outcomes of neocortical lesions at different postnatal ages in cats.
- To identify a potential critical period for optimal brain and behavioral restoration after injury.
- To explore the applicability of findings to other mammalian species.
Main Methods:
- Surgical resection of the left neocortex in cats at various postnatal ages (P10, P30, P60, P90, P120, and adulthood).
- Comprehensive neurobehavioral testing battery (16 tests) administered at least 6 months post-lesion.
- Statistical analysis to compare behavioral performance across different age-at-lesion groups.
Main Results:
- Cats lesioned between postnatal days 10 and 30 (P10-P30) exhibited significantly better behavioral recovery than those lesioned at older ages.
- A notable increase in behavioral impairments occurred between the P30 and P60 lesion age groups.
- A significant linear trend showed increasing impairment magnitude with older ages at lesion.
Conclusions:
- A critical maturational period (CMP), extending from fetal age 55 days to approximately P60, exists for optimal neocortical injury recovery in cats.
- This period of reduced vulnerability is hypothesized to be linked to specific developmental morphological events.
- The timing of the CMP in cats may be extrapolated to other higher mammals, including humans, suggesting conserved mechanisms of brain repair.
Abstract:
Groups of cats with resection of the neocortex of the left cerebral hemisphere at postnatal (P) ages (in days) 5-15 (P10), 30 (P30), 60 (P60), 90 (P90), 120 (P120), and in adulthood, were compared using a comprehensive battery of 16 neurobehavioral tests administered when they were at least 6 months post-lesion. For all behaviors, except 3 (including the paw contact placing reaction which never recovered), the performance was significantly better for the cats lesioned between P10 and P30 compared to cats lesioned at older ages. For 10 of the behaviors, the transition from age-at-lesion P30 to P60 was rather abrupt and characterized by a significant increment in impairments. However, cats with the resection at ages P90 and P120 still showed some behavioral advantage over the adult-lesioned animals. Overall, for most of the behaviors tested, there was a significant linear trend for an increase in the magnitude of impairments across the entire age-at-lesion range. We previously reported that cats with a unilateral frontal cortical lesion sustained during the late fetal life showed substantial behavioral impairments, while animals with a similar resection sustained early postnatally exhibited minimal abnormalities. These findings, together with the present results, indicate that the long-term behavioral outcome of neocortical injury is best when the lesion is sustained during a discrete period of the life of the cat. This period extends from about fetal age 55 days (the oldest lesion age in our fetal studies) to about P60, as shown in the present paper. For these reasons, we propose that there is a Critical Maturational Period (CMP) for optimal post injury brain and behavioral restoration. We hypothesize that this span of reduced vulnerability is linked to specific developmental morphological events which occur during the same time period. Since, as discussed, such ontogenetic events also occur in other mammal species (albeit at different chronological ages), we further propose that the timing of the CMP as delineated in cats, can be extrapolated to other higher mammals species including humans.
