TEMPORAL AND SPATIAL CHARACTERIZATION OF NEURONAL INJURY FOLLOWING LATERAL FLUID-PERCUSSION BRAIN INJURY IN THE RAT

The pattern of neuronal injury following lateral fluid-percussion (FP) brain injury in the rat was systematically characterized at sequentia l time points to identify selectively vulnerable regions and to determ ine the temporal contribution of primary and delayed neuropathological events. Male Sprague-Dawley rats (n = 28) were killed 10 min, 2 h, 12 h, 24 h, 4 days, and 7 days following a lateral FP brain injury of mo derate severity (2.2 arm), or 24 h after a sham injury. Brain sections were stained and analyzed using Nissl, acid fuchsin, and silver stain ing methods to identify regions with injured neurons or with visible l esions. Extensive numbers of acid fuchsin or silver-stained neurons we re observed as early as 10 min after the FP brain injury in regions ex tending from the caudate/putamen to the pens. The frequency of injured neurons was greatest in the ipsilateral cortex, hippocampus, and thal amus, and a visible loss of Nissl-stained neurons was observed in thes e regions beginning at 12 h after the FP brain injury. Acid fuchsin-st ained neurons were restricted to the same brain regions for all of the survival periods and gradually decreased in numbers between 24 h and 7 days after injury. These findings suggest that lateral FP brain inju ry in the rat produces a combination of focal cortical contusion and d iffuse subcortical neuronal injury, which is present within minutes of the impact, progresses to a loss of neurons by 12 h, and does not mar kedly expand into other brain regions with survival periods up to 7 da ys. Furthermore, the acute onset and rapid evolution of the neuronal i njury process may have important implications when considering a windo w of opportunity for pharmacological intervention.