Cerebrospinal fluid drainage kinetics across the cribriform plate are reduced with aging
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Fluids and Barriers of the CNS Open Access
RESEARCH
Cerebrospinal fluid drainage kinetics across the cribriform plate are reduced with aging Molly Brady1, Akib Rahman1, Abigail Combs1, Chethana Venkatraman1, R. Tristan Kasper2, Conor McQuaid1, Wing‑Chi Edmund Kwok3, Ronald W. Wood1,4 and Rashid Deane1,2*
Abstract Background: Continuous circulation and drainage of cerebrospinal fluid (CSF) are essential for the elimination of CSF-borne metabolic products and neuronal function. While multiple CSF drainage pathways have been identified, the significance of each to normal drainage and whether there are differential changes at CSF outflow regions in the aging brain are unclear. Methods: Dynamic in vivo imaging of near infrared fluorescently-labeled albumin was used to simultaneously visual‑ ize the flow of CSF at outflow regions on the dorsal side (transcranial and -spinal) of the central nervous system. This was followed by kinetic analysis, which included the elimination rate constants for these regions. In addition, tracer distribution in ex vivo tissues were assessed, including the nasal/cribriform region, dorsal and ventral surfaces of the brain, spinal cord, cranial dura, skull base, optic and trigeminal nerves and cervical lymph nodes. Results: Based on the in vivo data, there was evidence of CSF elimination, as determined by the rate of clearance, from the nasal route across the cribriform plate and spinal subarachnoid space, but not from the dorsal dural regions. Using ex vivo tissue samples, the presence of tracer was confirmed in the cribriform area and olfactory regions, around pial blood vessels, spinal subarachnoid space, spinal cord and cervical lymph nodes but not for the dorsal dura, skull base or the other cranial nerves. Also, ex vivo tissues showed retention of tracer along brain fissures and regions associated with cisterns on the brain surfaces, but not in the brain parenchyma. Aging reduced CSF elimina‑ tion across the cribriform plate but not that from the spinal SAS nor retention on the brain surfaces. Conclusions: Collectively, these data show that the main CSF outflow sites were the nasal region across the cribri‑ form plate and from the spinal regions in mice. In young adult mice, the contribution of the nasal and cribriform route to outflow was much higher than from the spinal regions. In older mice, the contribution of the nasal route to CSF outflow was reduced significantly but not for the spinal routes. This kinetic approach may have significance in deter‑ mining early changes in CSF drainage in neurological disorder, age-related cognitive decline and brain diseases. Keywords: CSF, Aging brain, Interstitial fluid (ISF), CSF outflow, CSF dynamics, Nasal/across the cribriform plate CSF drainage, Spinal nerves CSF drainage, Dural CSF drainage, CSF elimination rate constants
*Correspondence: [email protected] 1 Departments of Neuroscience, University of Rochester, URMC, 601 Elmwood Avenue, Rochester, NY 14642, USA Full list of author information is available at the end
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