Diagnostic Utility of Immunohistochemistry in Postmortem Detection of Acute Cerebral Hypoxic-Ischaemic Damage – A Systematic Review

Abstract

Acute hypoxic-ischemic brain injury (HIBI) is a crucial diagnostic challenge in forensic pathology, particularly in post-mortem examinations. The detection of HIBI is hindered by the limitations of traditional histopathological methods, which are often confounded by post-mortem changes such as tissue autolysis. Immunohistochemistry (IHC) has emerged as a valuable diagnostic tool, enabling more accurate detection of early neuronal injury markers, which could improve the differentiation of hypoxic-ischemic from traumatic brain injuries in autopsies. This systematic review aims to assess the diagnostic accuracy and forensic relevance of IHC markers in the post-mortem diagnosis of acute HIBI. A comprehensive literature search was conducted across multiple databases, including PubMed, Embase, and Scopus, focusing on studies published between 2000 and 2023. Studies were selected based on predefined eligibility criteria, and the risk of bias was assessed using the QUADAS-2 tool. The review summarizes pooled sensitivity and specificity estimates for key IHC markers, such as β-amyloid precursor protein (β-APP), heat shock protein 70 (HSP70), and hypoxia-inducible factor 1α (HIF-1α). The results indicate that β-APP and HSP70 exhibit high diagnostic accuracy for detecting acute HIBI in post-mortem brain tissue, particularly within the first few hours following death. The forensic significance of these markers lies in their potential to accurately estimate time of death and distinguish hypoxic-ischemic injuries from other causes of brain damage, aiding in legal determinations.