Mechanical injury and blood are drivers of spatial memory deficits after rapid intraventricular hemorrhage.
Autor: | Kamal K; Department of Neurological Surgery, UC Davis Medical Center, Sacramento, CA 95817, USA., Keiter JA; Psychiatry and Behavioral Sciences, UC Davis Medical Center, Sacramento, CA 95817, USA., Binyamin TR; Department of Neurological Surgery, UC Davis Medical Center, Sacramento, CA 95817, USA., de la Cruz Dapula JN; Department of Neurological Surgery, UC Davis Medical Center, Sacramento, CA 95817, USA., Vergara AR; Department of Neurological Surgery, UC Davis Medical Center, Sacramento, CA 95817, USA., Hawk CW; Department of Neurological Surgery, UC Davis Medical Center, Sacramento, CA 95817, USA., Izadi A; Department of Neurological Surgery, UC Davis Medical Center, Sacramento, CA 95817, USA., Lyeth B; Department of Neurological Surgery, UC Davis Medical Center, Sacramento, CA 95817, USA., Gurkoff GG; Department of Neurological Surgery, UC Davis Medical Center, Sacramento, CA 95817, USA., Sharp FR; Department of Neurology, UC Davis Medical Center, Sacramento, CA 95817, USA., Waldau B; Department of Neurological Surgery, UC Davis Medical Center, Sacramento, CA 95817, USA. Electronic address: bwaldau@ucdavis.edu. |
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Jazyk: | angličtina |
Zdroj: | Neurobiology of disease [Neurobiol Dis] 2020 Nov; Vol. 145, pp. 105084. Date of Electronic Publication: 2020 Sep 14. |
DOI: | 10.1016/j.nbd.2020.105084 |
Abstrakt: | Aneurysmal intraventricular hemorrhage (IVH) survivors may recover with significant deficits in learning and memory. The goal of this study was to investigate the mechanism of memory decline after intraventricular aneurysm rupture. We developed an aneurysmal IVH rat model by injecting autologous, arterial blood over the period of two minutes into the right lateral ventricle. We also evaluated the effects of a volume-matched artificial cerebrospinal fluid (CSF) control, thrombin and the mode of delivery (pulsed hand injection versus continuous pump infusion). We performed magnetic resonance brain imaging after 1 and 5 weeks to evaluate for hydrocephalus and histological analysis of the dentate gyrus after 6 weeks. Only animals which underwent a whole blood pulsed hand injection had a spatial memory acquisition and retention deficit 5 weeks later. These animals had larger ventricles at 1 and 5 weeks than animals which underwent a continuous pump infusion of whole blood. We did not find a decline in dentate gyrus granule cell neurons or an impairment in dentate gyrus neurogenesis or differentiation 6 weeks after IVH. Rapid injections of blood or volume resulted in microglial activation in the dentate gyrus. In conclusion, our results point to mechanical injury as the predominant mechanism of memory decline after intraventricular aneurysmal rupture. However, volume-matched pulsed injections of artificial CSF did not create a spatial memory deficit at 5 weeks. Therefore, whole blood itself must play a role in the mechanism. Further research is required to evaluate whether the viscosity of blood causes additional mechanical disruption and hydrocephalus through a primary injury mechanism or whether the toxicity of blood causes a secondary injury mechanism that leads to the observed spatial memory deficit after 5 weeks. Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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