Apoptotic changes in the cortex and hippocampus following minimal brain trauma in mice.
Interpretation of the cellular and molecular pathogenic basis of post-minimal traumatic brain injury is a significant clinical and scientific problem, especially due to the high prevalence of motor vehicle--and other accidents. Pathogenetic brain mechanisms following traumatic impact are usually investigated by using models of severe or moderate trauma. Apoptotic neuronal degeneration after notable brain trauma is a well-known phenomenon, but the source of its activation is not clear, especially after mild, subclinical brain trauma. In the present study, we used a closed head weight-drop model to induce minimal brain injury in mice. Pellets of 5, 10, 15, 20, 25 and 30 g were dropped on the right side of mice's head kept under light ether anesthesia. No abnormal behavioral or neurophysiological changes were seen following the head trauma. Morphological assessment was done 72 h after the traumatic impact using TUNEL assay and silver staining. We found gradual increase of TUNEL-positive and silver-impregnated cells number in different cortical and hippocampal regions of both injured and contralateral hemispheres. The threshold of traumatic impact that caused a significant activation was 10-15 g pellets (evident by silver staining), and 15-20 g for apoptosis. The most sensitive zones for trauma were anterior cingulate cortex and CA3 area of hippocampus. No bilateral hemispheric differences were found. Our results demonstrate that even closed head minimal traumatic brain injury can cause diffused neuronal damage and apoptosis. This results correlate well with cognitive and behavioral deficits described for mice suffering similar mTBI and can also explain the wide variety of mental disturbances described for post-concussion syndrome in patients who suffered mild head injury.
Tashlykov
Vadim
V
Laboratory of Anesthesia, Pain and Neural Research, Bruce Rapaport Medical Faculty, Technion Israel Institute of Technology, Haifa, Israel.
Katz
Yeshayahu
Y
Gazit
Vered
V
Zohar
Ofer
O
Schreiber
Shaul
S
Pick
Chaim G
CG
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001930:Brain Injuries / Q000473:pathology*; D002540:Cerebral Cortex / Q000293:injuries / Q000473:pathology*; D004195:Disease Models, Animal; D016489:Head Injuries, Closed / Q000473:pathology; D006624:Hippocampus / Q000293:injuries / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009410:Nerve Degeneration / Q000473:pathology*; D012720:Severity of Illness Index