Lateral fluid percussion injury in the developing rat causes an acute, mild behavioral dysfunction in the absence of significant cell death.
Lateral fluid percussion injury (LFP), a model of mild-moderate concussion, leads to the temporary loss of the capacity for experience-dependent plasticity in developing rats. To determine if this injury-induced loss in capacity for plasticity is due to cell death, we conducted stereological measurements within the cerebral cortex and CA3 of the hippocampus 2 weeks following mild, moderate or severe LFP in the post-natal day 19 (P19) rat. Results indicated that there was no significant change in the absolute number of neurons, regardless of injury severity, in either the ipsilateral cortex (sham = 10.6 +/- 1.7, mild = 11.5 +/- 2.1, moderate = 10.0 +/- 1.0, severe = 10.9 +/- 1.3 million neurons) or CA3 region of the hippocampus (sham = 251 +/- 38, mild = 289 +/- 2, moderate = 245 +/- 48, severe = 255 +/- 62 thousand neurons). Even though there was no evidence of a significant degree of injury-induced cell death, animals exhibited cognitive deficits as revealed in a Morris water maze task (MWM). The MWM results indicated that regardless of injury severity, P19-injured rats exhibited a significant increase in escape latency compared to age-matched shams (injury by day; P < 0.001) and a significant increase in the number of trials needed to reach criterion (P < 0.05). Analysis of a probe trial one week post-MWM training, however, indicated that there was no deficit in storage or recall of the learned behavior as analyzed by platform hits (sham = 2.9 +/- 0.37, mild = 2.0 +/- 0.40, moderate = 1 +/- 0, severe = 2.8 +/- 0.62) or percent time spent in, or immediately surrounding, the platform area (sham = 13.5 +/- 1.71, mild = 10.8 +/- 2.32, moderate = 12.7 +/- 0, severe = 13.5 +/- 1.69). Taken together, these results indicate that while LFP in P19-injured animals does not lead to significant cell death, it does generate acute, mild deficits in MWM performance.
Division of Neurosurgery, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-7039, USA. ggurkoff@ucla.edu
Gene G
GG
Gurkoff
Christopher C
CC
Giza
David A
DA
Hovda
D000367:Age Factors; D000818:Animals; D001924:Brain Concussion / Q000473:pathology* / Q000503:physiopathology; D002452:Cell Count; D016923:Cell Death / Q000502:physiology; D002540:Cerebral Cortex / Q000254:growth & development / Q000293:injuries / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000254:growth & development / Q000293:injuries / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D009474:Neurons / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric