title: Long-term functional consequences and ongoing cerebral inflammation after subarachnoid hemorrhage in the rat.
abstract: Subarachnoid hemorrhage (SAH) represents a considerable health problem with an incidence of 6-7 per 100.000 individuals per year in Western society. We investigated the long-term consequences of SAH on behavior, neuroinflammation and gray- and white-matter damage using an endovascular puncture model in Wistar rats. Rats were divided into a mild or severe SAH group based on their acute neurological score at 24 h post-SAH. The degree of hemorrhage determined in post-mortem brains at 48 h strongly correlated with the acute neurological score. Severe SAH induced increased TNF-α, IL-1β, IL-10, MCP-1, MIP2, CINC-1 mRNA expression and cortical neutrophil influx at 48 h post-insult. Neuroinflammation after SAH was very long-lasting and still present at day 21 as determined by Iba-1 staining (microglia/macrophages) and GFAP (astrocytes). Long-term neuroinflammation was strongly associated with the degree of severity of SAH. Cerebral damage to gray- and white-matter was visualized by immunohistochemistry for MAP2 and MBP at 21 days after SAH. Severe SAH induced significant gray- and white-matter damage. MAP2 loss at day 21 correlated significantly with the acute neurological score determined at 24 h post-SAH. Sensorimotor behavior, determined by the adhesive removal task and von Frey test, was affected after severe SAH at day 21. In conclusion, we are the first to show that SAH induces ongoing cortical inflammation. Moreover, SAH induces mainly cortical long-term brain damage, which is associated with long-term sensorimotor damage.
authors.affiliation: Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands; Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Elke
authors.initials: E
authors.lastname: Kooijman
authors.affiliation: Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Cora H
authors.initials: CH
authors.lastname: Nijboer
authors.affiliation: Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Cindy T J
authors.initials: CT
authors.lastname: van Velthoven
authors.affiliation: Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: Mol
authors.affiliation: Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Rick M
authors.initials: RM
authors.lastname: Dijkhuizen
authors.affiliation: Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jozef
authors.initials: J
authors.lastname: Kesecioglu
authors.affiliation: Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands; Department of Symptom Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Cobi J
authors.initials: CJ
authors.lastname: Heijnen
mesh_terms: D000818:Animals; D001925:Brain Damage, Chronic / Q000276:immunology; D002540:Cerebral Cortex / Q000276:immunology / Q000473:pathology*; D004660:Encephalitis / Q000276:immunology / Q000503:physiopathology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000276:immunology; D011596:Psychomotor Disorders / Q000276:immunology; D017208:Rats, Wistar; D020127:Recovery of Function; D013345:Subarachnoid Hemorrhage / Q000276:immunology / Q000503:physiopathology*