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

Figure 2

Impairment in brain lymphatic drainage and the formation of cerebral edema. The meningeal lymphatic system constitutes the brain lymphatic drainage system in the dorsal part of the skull and the glymphatic system (a glia-dependent system of the perivascular space) present in the brain parenchyma. The meningeal lymphatics are involved in maintaining homeostasis and immune surveillance in the brain. The glymphatic system provides a pathway to remove interstitial solutes and wastes in the brain parenchyma. It is also a bidirectional exchange pathway between ISF and CSF. However, the meningeal lymphatic system may only function as a drainage pathway. The brain lymphatic drainage system is a crucial drainage route for ISF/CSF into the cervical lymph nodes (CLNs) or peripheral blood. Brain injury may alter the drainage function of the meningeal lymphatic system and glymphatic system and subsequently aggravate brain edema after ischemic stroke, subarachnoid hemorrhage, TBI, etc. High ICP may reduce the flow of the lymphatic system from the ISF/CSF to the CLN or the venous sinus. Impairment in the glia-dependent system of the perivascular space, especially dislocation of AQP4 in the endfeet of the astrocyte of the glymphatic system, can lead to an increase in ISF/CSF influx to the brain parenchyma with a decrease in efflux from the brain parenchyma to ISF/CSF or CLN/blood. Reduction in the function of the lymphatic and glymphatic systems can also lead to a decrease in waste clearance and an increase in immunocyte accumulation in the injured brain. Although animal studies have indicated that brain lymphatic drainage dysfunction may facilitate the formation of brain edema after ICH, no studies have explored its relationship in patients with ICH. Abbreviations: CSF: cerebrospinal fluid; ISF: interstitial fluid; CLNs: cervical lymph nodes; TBI: traumatic brain injury; ICP: intracranial pressure; AQP4: aquaporin 4; ICH: intracerebral hemorrhage.