The glymphatic-lymphatic fluid transport system (GLFTS) consists of glymphatic pathway and cerebrospinal fluid (CSF) lymphatic outflow routes, allowing biological liquids from the brain parenchyma to access the CSF along with perivascular space and to be cleaned out of the skull through lymphatic vessels. It is known that increased local pressure due to physical compression of tissue improves lymphatic transport in peripheral organs, but little is known about the exact relationship between increased intracranial pressure (IICP) and GLFTS. In this study, we verify our hypothesis that IICP significantly impacts GLFTS, and this effect depends on severity of the IICP. Using a previously developed inflating balloon model to induce IICP and inject fluorescent tracers into the cisterna magna, we found significant impairment of the glymphatic circulation after IICP. We further found that cerebrovascular occlusion occurred, and cerebrovascular pulsation decreased after IICP. IICP also interrupted the drainage of deep cervical lymph nodes and dorsal meningeal lymphatic function, enhancing spinal lymphatic outflow to the sacral lymph nodes. Notably, these effects were associated with the severity of IICP. Thus, our findings proved that the intensity of IICP significantly impacts GLFTS. This may have translational applications for preventing and treating related neurological disorders.
The persistent dysregulation and accumulation of poisonous proteins from destructive neural tissues and cells activate pathological mechanisms after traumatic brain injury (TBI). The lymphatic drainage system of the brain, composed of the glymphatic system and meningeal lymphatic vessels (MLVs), plays an essential role in the clearance of toxic waste after brain injury. The neuroprotective effect of interleukin 33 (IL-33) in TBI mice has been demonstrated; however, its impact on brain lymphatic drainage is unclear. Here, we established a fluid percussion injury model to examine the IL-33 administration effects on neurological function and lymphatic drainage in the acute brain of TBI mice. We verified that exogenous IL-33 could improve the motor and memory skills of TBI mice and demonstrated that in the acute phase, it increased the exchange of cerebrospinal and interstitial fluid, reversed the dysregulation and depolarization of aquaporin-4 in the cortex and hippocampus, improved the drainage of MLVs to deep cervical lymph nodes, and reduced tau accumulation and glial activation. We speculate that the protective effect of exogenous IL-33 on TBI mice’s motor and cognitive functions is related to the enhancement of brain lymphatic drainage and toxic metabolite clearance from the cortex and hippocampus in the acute stage. These data further support the notion that IL-33 therapy may be an effective treatment strategy for alleviating acute brain injury after TBI.
AimWe aimed to assess the effects of cerebral glucagon‐like peptide‐1 receptor (GLP‐1R) activation on the glymphatic system and whether this effect was therapeutic for traumatic brain injury (TBI).MethodsImmunofluorescence was employed to evaluate glymphatic system function. The blood–brain barrier (BBB) permeability, microvascular basement membrane, and tight junction expression were assessed using Evans blue extravasation, immunofluorescence, and western blot. Immunohistochemistry was performed to assess axonal damage. Neuronal apoptosis was evaluated using Nissl staining, terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling (TUNEL) staining, and western blot. Cognitive function was assessed using behavioral tests.ResultsCerebral GLP‐1R activation restored glymphatic transport following TBI, alleviating BBB disruption and neuronal apoptosis, thereby improving cognitive function following TBI. Glymphatic function suppression by treatment using aquaporin 4 inhibitor TGN‐020 abolished the protective effect of the GLP‐1R agonist against cognitive impairment.ConclusionCerebral GLP‐1R activation can effectively ameliorate neuropathological changes and cognitive impairment following TBI; the underlying mechanism could involve the repair of the glymphatic system damaged by TBI.
Prognostic factors in patients with primary chronic subdural hematoma (CSDH) taking the natural course are unclear. To identify independent influencing factors of wait-and-watch management, a case–control study of moderate CSDH patients using wait-and-watch as monotherapy in a single center from February 2014 to November 2021 was conducted. A total of 39 patients who responded to wait-and-watch management (cases) and 24 nonresponders (controls) matched for age, sex, height, weight, MGS-GCS (Markwalder grading scale and Glasgow Coma Scale), and bilateral hematoma were included. Demographics, blood cell counts, serum biochemical levels, imaging data, and relevant clinical features at baseline were collected. Significant differences between cases and controls were found in the hematoma volume, ability to urinate, maximal thickness of the hematoma, and hypodensity of the hematoma in univariate analysis. Hypodense hematoma and hematoma volume were independently associated with the outcome in multivariate analysis. Combining these independently influencing factors revealed an area under the receiver operator characteristic curve of 0.741 (95% CI: 0.609-0.874, sensitivity = 0.783, specificity = 0.667). These findings may contribute to the early detection of patients with moderate CSDH who may respond to wait-and-watch strategies. Although wait-and-watch tactics could work sometimes, medical interventions, including drug treatment, should be recommended in the clinic.
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