Quantifying glymphatic system efflux following rmTBI
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Zhang, Daniel
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Abstract
Traumatic brain injury (TBI) is a leading cause of death and injury that can lead to long-term health problems and decreased quality of life and has been shown to alter glymphatic clearance in preclinical and clinical TBI. This study aims to measure glymphatic system efflux by measuring brain clearance 24 hours post-injury. Male Sprague Dawley rats were divided into TBI (nTBI = 10) and Sham (nSham = 10) groups. TBI animals obtained 3 closed head impacts at a velocity of 5 m/s at displacements 5, 2, and 2 mm in 2-minute intervals. Radiolabeled tracers containing 0.05 μCi of [14C]-inulin-carboxyl (5000 Da) and [3H]-sucrose (342 Da) in 5 μL of artificial cerebrospinal fluid buffer (aCSF) were injected into the striatum 24 hours post-injury. Blood was collected at 30, 60, 90, and 120 minutes and the lymph nodes, brains, olfactory bulbs (OBs), nasopharynx (NP), and CSF were extracted at 120 minutes post-infusion. The brains were sectioned coronally into 5 mm sections anterior to posterior (BR1, 2, 3, 4). Samples were then solubilized and counted with a liquid scintillation counter (LSC). A small injury effect was observed, as evidenced by a significant increase in normalized counts [14C]-inulin-carboxyl in BR2 for TBI vs. Sham groups, indicating reduced glymphatic clearance from the injection site. Additionally, there were significant levels of both [14C]-inulin-carboxyl and [3H]-sucrose in the CSF, which suggests preferential glymphatic clearance over the blood-brain barrier (BBB). Clearance from the brain was also found to be dependent on tracer size. The low recovery of [3H]-sucrose in the whole animal suggests it may have been distributed to an unknown area or possibly excreted through feces or urine. This study is only focused on a single time point, so injury effects may be more pronounced at other time points, and further studies looking at other times are needed to have a more concrete model of the efflux routes of the glymphatic system.
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2024-07-30
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