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Neuropathol Appl Neurobiol. 2007 Apr;33(2):226-37.

Traumatic axonal damage in the brain can be detected using beta-APP immunohistochemistry within 35 min after head injury to human adults.

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Department of Clinical Neuropathology, King's College Hospital, London, UK.


Immunohistochemistry staining for beta-amyloid precursor protein (beta-APP) is a sensitive method to detect early axonal damage in traumatic brain injury, which was previously estimated to be of minimum 60-90 min after head injury. We present seven cases of well-documented posttraumatic survival of 35-60 min where beta-APP detects early axonal damage. Cases were selected from routine work where documentation about survival is judged to be accurate. These are divided into three groups: group 1: severe head injury (n = 7) with documented survival between 35 and 60 min. Group 2: severe head injury (n = 4) with documented survival of less than 30 min. Group 3: cases (n = 4) where death was not due to head injury but survival is documented between 45 and 109 min. The brains were fixed in formalin for 4 weeks and six regions (frontal lobe with anterior corpus callosum, parietal lobe with deep white matter, basal ganglia with posterior limb of internal capsule, cerebellum with white matter and middle cerebellar peduncle and pons with basis pontis and superior cerebellar peduncle) were sampled. All blocks were stained for haematoxylin and eosin and beta-APP and selected ones for CD68, using antigen retrieval method. In group 1 sections revealed beta-APP immunoreactivity in forms of small globules and granules and occasionally as thin and short filaments. These were detected in the pons, corpus callosum, internal capsule and cerebral white matter, with some variation in localization and intensity. In groups 2 and 3 all the sections were negative for beta-APP staining. None of the cases showed evidence of severe brain swelling, increased intracranial pressure, ischaemia or infection. Using the antigen retrieval method, beta-APP immunohistochemistry can detect axonal damage within 35 min after severe head injury. These results may have an implication in the consideration of minimal survival time after traumatic head injury in medico-legal practice.

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