Survivors of intraventricular hemorrhage are often left with significant long-term memory impairment; thus, research utilizing intraventricular hemorrhage animal models is essential. In this study, we sought out ways to measure intracranial pressure, mean arterial pressure, and cerebral perfusion pressure during nontraumatic intraventricular hemorrhage in rodents. The experimental design included three Sprague Dawley groups: sham, standard 200 µl intraventricular hemorrhage, and vehicle control groups. By introducing an intraparenchymal fiberoptic pressure sensor, precise intracranial pressure measurements were obtained in all groups. Cerebral perfusion pressures were calculated with the knowledge of intracranial pressure and mean arterial pressure values. As expected, the intraventricular hemorrhage and vehicle control groups both experienced a rise in the intracranial pressure and subsequent decline in cerebral perfusion pressure during intraventricular injection of autologous blood and artificial cerebrospinal fluid, respectively. The addition of an intraparenchymal fiberoptic pressure sensor is beneficial in monitoring precise intracranial pressure changes.

Mechanisms underlying memory and cognitive dysfunction following spontaneous intracranial hemorrhage are diverse. The aim of this systematic review was to provide a contemporary review of the commonly reported mechanisms responsible for memory impairment following nontraumatic intracranial hemorrhage. PubMed, Embase, and Scopus databases were systematically searched for pre-clinical studies, and results were reported according to PRISMA guidelines. Methodological quality assessment was performed according to the SYRCLE's Risk of Bias tool. Ninety studies met the inclusion criteria. Most of animal studies reported on subarachnoid hemorrhage (48%), followed by intraparenchymal hemorrhage (44%), and intraventricular hemorrhage (8%). Most of subarachnoid hemorrhage studies (30%) reported neuronal apoptosis as a mechanism for memory dysfunction, whereas the most commonly described mechanism following intraparenchymal hemorrhage (40%) and intraventricular hemorrhage (23%) was a proinflammatory response. Based on SYRCLE's Risk of Bias assessment, the average methodological risk of bias of all studies was 56.83 ± 12.77% on a 0-100% scale. There is a great need not only for more preclinical studies with improved methodology, but also for studies reporting negative treatment effects and for multicenter animal studies. In vivo studies on non-rodent animal ICH models can also be helpful.

Traumatic Brain Injury (TBI) is a major source of mortality worldwide. Survivors of moderate-to-severe TBI frequently have neurological and cognitive deficits. There are no pharamacological therapeutics for neuroprotection following TBI.

The mechanisms of cognitive decline after intraventricular hemorrhage (IVH) in some patients continue to be poorly understood. Multiple rodent models of intraventricular or subarachnoid hemorrhage have only shown mild or even no cognitive impairment on subsequent behavioral testing. In this study, we show that intraventricular hemorrhage only leads to a significant spatial memory deficit in the Morris water maze if it occurs in the setting of an elevated intracranial pressure (ICP). Histopathological analysis of these IVH + ICP animals did not show evidence of neuronal degeneration in the hippocampal formation after 2 weeks but instead showed significant microglial activation measured by lacunarity and fractal dimensions. RNA sequencing of the hippocampus showed distinct enrichment of genes in the IVH + ICP group but not in IVH alone having activated microglial signaling pathways. The most significantly activated signaling pathway was the classical complement pathway, which is used by microglia to remove synapses, followed by activation of the Fc receptor and DAP12 pathways. Thus, our study lays the groundwork for identifying signaling pathways that could be targeted to ameliorate behavioral deficits after IVH.