Molecular, Pathological, Clinical, and Therapeutic Aspects of Perihematomal Edema in Different Stages of Intracerebral Hemorrhage

Abstract

Acute intracerebral hemorrhage (ICH) is a devastating type of stroke worldwide. Neuronal destruction involved in the brain damage process caused by ICH includes a primary injury formed by the mass effect of the hematoma and a secondary injury induced by the degradation products of a blood clot. Additionally, factors in the coagulation cascade and complement activation process also contribute to secondary brain injury by promoting the disruption of the blood-brain barrier and neuronal cell degeneration by enhancing the inflammatory response, oxidative stress, etc. Although treatment options for direct damage are limited, various strategies have been proposed to treat secondary injury post-ICH. Perihematomal edema (PHE) is a potential surrogate marker for secondary injury and may contribute to poor outcomes after ICH. Therefore, it is essential to investigate the underlying pathological mechanism, evolution, and potential therapeutic strategies to treat PHE. Here, we review the pathophysiology and imaging characteristics of PHE at different stages after acute ICH. As illustrated in preclinical and clinical studies, we discussed the merits and limitations of varying PHE quantification protocols, including absolute PHE volume, relative PHE volume, and extension distance calculated with images and other techniques. Importantly, this review summarizes the factors that affect PHE by focusing on traditional variables, the cerebral venous drainage system, and the brain lymphatic drainage system. Finally, to facilitate translational research, we analyze why the relationship between PHE and the functional outcome of ICH is currently controversial. We also emphasize promising therapeutic approaches that modulate multiple targets to alleviate PHE and promote neurologic recovery after acute ICH.

Radiomics features from perihematomal edema for prediction of prognosis in the patients with basal ganglia hemorrhage

“…Volbers et al ( 37 ) showed that the volume of PHE is an independent predictive factor for ICH patients at 90 days post-onset. However, it has controversy for the connection between PHE and the ICH patients' outcome ( 38 ). Loan et al ( 39 ) reported the volume of PHE was not independently associated with death or dependence 1 year after ICH, as well as the total volume of ICH and PHE are independent risk factors.…”

Relationship between edema and intracranial pressure following intracerebral hemorrhage in rat

“…Indeed, in human patients, an increase in ICP variability along with a greater amount of time spent above 20 mmHg are both significantly associated with a greater risk of death or disability following ICH, emphasizing the importance of better understanding intracranial compliance as a treatment target (Tian et al, 2013;Al-Kawaz et al, 2021). In the early hours during and following acute bleeding, cerebrovascular autoregulation, CSF and glymphatic circulation, and cellular volume homeostasis become dysregulated due to the hematoma, cerebral edema, and associated mechanical damage (Hoff and Xi, 2003;Chen et al, 2015;Faragó et al, 2016;Bothwell et al, 2019;Jiang et al, 2022). Following ICH, edema develops via three distinct mechanistic phases: (1) cytotoxic edema, (2) ionic edema, and (3) vasogenic edema (Hoff and Xi, 2003;Stokum et al, 2016;Wan et al, 2023).…”

The Implications of Microglial Regulation in Neuroplasticity-Dependent Stroke Recovery

“…Hematomas compressing brain tissue form for blood leakage into the brain parenchyma. The mass effect of the hematoma combined with neurotoxic effects further causes increased intracranial pressure, cerebral herniation, or death [ 14 , 15 ].…”