**3.2. Diffuse brain injury**

252 Apoptosis and Medicine

Open skull fractures with brain lacerations

Brain contusions/ SAH/SDH without brain swelling or compression sign

Brain contusions/ SAH/SDH with brain swelling and compression sign

Brain contusions/ SAH/SDH with brain swelling and compression sign with craniotomy

with regard to the survival time

without craniotomy

Macropathology Peracute death

ST, minutes

Decreased white matter astrocyte GFAP positivity

Acute death ST <0.5 h

Decreased white matter astrocyte GFAP positivity

Increased cortical astrocyte bFGF positivity

Subacute death ST, 0.5–12 h


Increased cortical and white matter astrocyte bFGF positivity

Cortical and

ST, survival time; SAH, subarachnoid hemorrhage; SDH, subdural hemorrhage or hematoma; ssDNA, single-stranded

**Table 1.** Immunohistochemical findings of apoptosis-related biomarkers in mechanical brain injury

DNA, bFGF, basic fibroblast growth factor; GFAP, glial fibrillary acidic protein

Early death ST, 12 h–3 days

cortical and white matter bFGF positivity


+ hippocampal involvement and partly low GFAP positivity

white matter astrocyte loss with decreased GFAP positivity and neuronal

with increased ssDNA positivity

loss

with hippocampal involvement

Prolonged death ST >3 days


Diffuse astrocyte loss with decreased GFAP positivity

and

neuronal loss with increased ssDNA positivity

Diffuse mechanical brain injury clinically involves primary and secondary CNS dysfunction, which may result in permanent disability or fatal outcome. This type of mechanical brain injury is morphologically associated with specific white matter injury, usually termed diffuse axonal injury (DAI); however, other non-specific factors, including disrupted BBB, ischemia and vascular injury, also contribute to posttraumatic CNS dysfunction (Oehmichen et al., 2006). The macropathology may present with brain swelling and hemorrhages in the deep part of white matter, for which histology often involves focal edema and demyelination, accompanied by axonal injury, along the junction of gray and white matter, but these findings cannot be detected in very short survival cases. In such cases of peracute or instantaneous death within minutes, involving severe open head injury and apparently fatal structural brain damage, immunohistochemistry detected decreased glial GFAP positivity in the parietal white matter without glial or neuronal loss; however, this finding was not evident in the cerebral cortex (Wang et al., 2012b). GFAP as a marker of fibrous astrocytes in the white matter and molecular layer of the cerebral cortex is usually not detectable in protoplasmatic astrocytes or neurons in the cerebral cortex by routine immunohistochemistry (Li et al., 2009b). An increase in GFAP immunoreactivity in the cerebral cortex may be detected in classic astrocytic activation or astrogliosis; however, GFAP immunopositivity in the cerebral cortex showed no difference among all mechanical brain injury and control groups, irrespective of survival times, indicating a morphologically intact cerebral cortex. In peracute death, however, a significant decrease of white matter GFAP immunopositivity indicated the immediate, diffuse disruption of brain white matter; such findings were not detected in the hippocampus. Similar findings were detected in acute and subacute deaths (survival time <12 h) due to closed head injury without parahippocampal hernia as a brain compression sign, irrespective of the type of brain injury. This glial change in the parietal white matter may represent damage to the whole brain white matter immediately due to mechanical brain injury, suggesting fatal CNS dysfunction without brain swelling (Graham et al., 1988).
