P-selectin-positive microthrombi in traumatic brain injury: an immunohistochemical study

Traumatic brain injury (TBI) is characterized by complex secondary injury mechanisms, including microvascular dysfunction and platelet/endothelial activation. The formation of microthrombi within the cerebral microcirculation has been proposed as a contributing factor to secondary brain damage, but its characterization in human post-mortem tissue remains limited. This retrospective study included 30 cases of fatal TBI resulting from road traffic accidents and 13 non-traumatic controls without evidence of cranial or parenchymal brain pathology. Brain samples were collected during medico-legal autopsy and analyzed using immunohistochemistry for P-selectin (CD62P). Microthrombi were evaluated using a semi-quantitative approach based on 12 non-overlapping microscopic fields per section. Cases were grouped according to survival intervals. P-selectin-positive microthrombi were detectable at early stages after trauma, including within the first hour. Their number increased in the early post-traumatic period, with the highest values observed within 4-48 h, followed by a progressive decline at longer survival intervals. Morphological analysis showed a transition from P-selectin-positive aggregates compatible with early platelet/endothelial activation to thrombotic formations with an increasing cellular component morphologically compatible with leukocytes over time. Control cases showed minimal or absent P-selectin expression, with significantly lower counts than TBI cases. P-selectin-positive microthrombi can be identified in human post-mortem brain tissue following TBI and show a time-related distribution, supporting the involvement of platelet/endothelial activation and thromboinflammatory microvascular alterations in secondary brain injury. Further studies are needed to validate these findings and to better define their specificity, temporal significance, and forensic applicability.