Temporal profile of apoptotic-like changes in neurons and astrocytes following controlled cortical impact injury in the rat

Apoptotic cell death has been observed in both neurodegenerative diseases a nd acute neurological traumas such as ischemia, spinal cord injury, and tra umatic brain injury (TBI). Recent studies employing different models of TBI have described morphological and biochemical changes characteristic of apo ptosis following injury However, no study has examined the temporal profile of apoptosis following controlled cortical impact (CCI) injury in the rat. In addition, the relative frequency of apoptotic profiles in different cel l types (neurons versus glia) following CCI has yet to be investigated. In the present experiments, injured cortex was subjected to DNA electrophoresi s, and serial sections from the contusion area were stained with hematoxyli n and eosin or Hoechst 33258 or double-labeled with TUNEL and neuronal or g lial markers. The results of the present study indicate that CCI produces a substantial amount of DNA damage associated with both apoptotic-like and n ecrotic-like cell death phenotypes primarily at the site of cortical impact and focal contusion. DNA damage, as measured by TUNEL and DNA electrophore sis, was most apparent 1 day following injury and absent by 14 days post-TB I. However, quantitative analysis showed that the majority of TUNEL-positiv e cells failed to exhibit apoptotic-like morphology and were probably under going necrosis. In addition, apoptotic-like morphology was predominantly ob served in neurons compared to astrocytes. The present study provides furthe r evidence that apoptosis is involved in the pathology of TBI and could con tribute to some of the ensuing cell death following injury. (C) 1999 Academ ic Press.