Capillary stalling after traumatic brain injury: an emerging microcirculatory contributor to secondary brain injury

Secondary brain injury after traumatic brain injury (TBI) has traditionally been understood and managed through the lens of intracranial pressure, cerebral perfusion pressure, and global cerebral blood flow. Yet a substantial proportion of patients continue to exhibit persistent tissue hypoxia and metabolic crisis even when these macrocirculatory parameters appear adequately controlled. Capillary stalling-the transient or sustained interruption of red blood cell transit within individual or focal capillary networks-may represent an under-recognized microcirculatory disorder that conventional macrovascular monitoring cannot capture. This review synthesizes evidence supporting capillary stalling as a potentially distinct and reversible component of post-traumatic microvascular failure. We examine candidate mechanisms of capillary flow interruption after TBI, including endothelial injury and glycocalyx disruption, leukocyte plugging, pericyte contraction, platelet activation and microthrombosis, red blood cell dysfunction, and edema-associated extravascular compression. These mechanisms can generate marked capillary flow heterogeneity, impair oxygen extraction, and contribute to metabolic crisis, neuroinflammation, and secondary neuronal injury. We further discuss why conventional bedside monitoring-including intracranial pressure, cerebral perfusion pressure, global cerebral blood flow, brain tissue oxygenation, and microdialysis-may fail to detect capillary-level flow abnormalities, and we review established and emerging detection strategies from experimental two-photon microscopy to clinical surrogates. Finally, we evaluate potential microcirculation-targeted therapeutic avenues. Direct evidence of capillary stalling in human TBI remains limited; accordingly, it should currently be viewed as a biologically plausible and testable contributor to secondary brain injury rather than an established dominant driver.