Motor and cognitive deficits in apolipoprotein E-deficient mice after closed head injury
Section snippets
Induction of closed head injury
ApoE-knockout mice and control mice from the same parent litter were kindly provided by Dr J. L. Breslaw.[18]CHI was induced under ether anaesthesia, confirmed by testing corneal and pupillary reflexes, in four-month-old male apoE-deficient (n=18) and control (n=12) mice weighing 30–36 g. In brief, trauma was caused by a modified electric weight-drop device[2]that was allowed to free-fall until the silicone tip (diameter 3 mm) hit the exposed skull on the left cerebral hemisphere, ∼1–2 mm lateral
Clinical evaluation
The neurological status of the injured mice was evaluated by measuring NSS at different intervals following CHI. As can be seen (Fig. 1), the two groups displayed a similar NSS at 1 h, indicating similar severity of injury. They also showed parallel recovery during the first week following CHI, the NSS reaching a value of ∼12. However, there were marked differences between the two groups in the extent of their subsequent recovery. Whereas the control mice (n=12) gradually and persistently
Discussion
The results of the present study demonstrate that apoE-deficient mice show greater cognitive and neurological derangement than do control mice for up to at least 40 days following CHI. These disturbances were associated with more pronounced neuronal cell death in the hippocampus of the apoE-deficient mice. The paradigm of injury and the early (within 1 h of CHI) damage were essentially similar in the two groups of mice, as evidenced by the similar NSS at 1 h, suggesting that the increased
Conclusions
The present results show that apoE-deficient mice are highly susceptible to the sequalae of head trauma and suggest that the increased vulnerability is due to defects in apoE-dependent neuronal repair mechanisms. This model may replicate head trauma-related pathogenic processes and provide a useful tool for studying the synergistic effects of traumatic head injury and ApoE in the development of AD.
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