traumatic brain injury

Does Traumatic Brain Injury Trigger Delayed Neuronal Death through Apoptosis?


Background: There are conflicting data on the role that apoptosis plays in traumatic brain injury (TBI). Models by different investigators differed in species, age, mechanism/severity of injury, and morphologic documentation of neuronal cell death.
Objective: Determine if injury severity is a trigger of apoptotic cell death in juvenile mice.


Twelve 10-week-old male C57Bl/6 wild-type mice were divided into 2 groups of 6. Anesthetized animals were placed in a stereotactic head-holder. The scalp was incised and the lambdoid suture identified. An electromagnetic impactor with a metallic tip was set to deliver an impact at 3.1 ± 0.1 m/sec, 20% from perpendicular, centered 3 mm anterior and 2 mm left-lateral of lambda. Indentation depth was set at 2 mm. The two groups differed only in that group 1 was impacted with a 3-mm tip, and group 2 with a 6-mm tip. Following impact, the mice were recovered to wakefulness. Histology using silver/cupric nitrate and anti-caspase-3 staining was performed at 24 hours.
Results: No mice impacted with the 6-mm tip displayed skull fracture or hemorrhage. All recovered consciousness within 2 minutes and interacted normally. Silver stain indicative of neuronal cell damage was confined mostly to layer 1-3 of the ipsilateral parietal cortex. None displayed caspase 3 immunostaining. All mice impacted with the 3-mm tip had localized skull fracture and subarachnoid hemorrhage. They had prolonged unconsciousness (>5 minutes) and decreased motor activity. Five animals survived 24 hours. Histologic examination (silver staining) showed bilateral neuronal injury in the parietal cortex, hippocampus, and thalamus. Caspase 3 positive cells were seen in the penumbra and ipsilateral hippocampus.


These results confirm apoptosis is present at 24 hours in animals with moderate to severe TBI, but not with mild TBI. Further work is needed to define the threshold of injury at which apoptosis plays an important role in secondary neuronal death.