Intracranial Pressure Changes in Rat Models of Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is a devastating subtype of stroke but the role of increased intracranial pressure (ICP) in ICH is unclear - especially since most studies measure ICP in rodents tethered or under anesthesia or restraint. Thus, ICP was measured using telemetry in untethered, awake rats after ICH for 4 days. In PART 1, no pressure differences were found between the site of injury and epidural space. In PART 2, a severe ICH increased ICP for 4 days with modest reductions in cerebral perfusion pressure. In PART 3, moderate to severe ICHs were compared in different models of ICH. When ICH was induced by a collagenase infusion, ICP was increased for 2 days. However, ICP did not increase when the ICH was induced by a whole blood infusion. Lastly, increases in edema correlated with increases in ICP. These findings demonstrate ICH model differences that must be considered when evaluating therapies

Intracranial pressure measured in freely moving rats for days after intracerebral hemorrhage

AbstractIn some patients, intracerebral hemorrhage (ICH) causes life-threatening elevations in intracranial pressure (ICP) arising from mass effect of the hematoma and edema. Accordingly, edema is a common endpoint to gauge treatment efficacy in rodent ICH models. Despite widespread reliance on edema, its relationship with ICP and cerebral perfusion pressure (CPP) is unknown. Blood pressure (BP) and ICP were measured by telemetry devices in rats after collagenase (“severe” — 0.3U, and “moderate” — 0.15U doses) or blood infusion (100μL) into striatum (vs. saline infused shams). We compared epidural and intraparenchymal ICP readings (collagenase), evaluated CPP (collagenase), and compared models. Moderate (9.46mmHg±4.72 SD, 3day average) and severe collagenase ICHs (10.79±3.50) significantly increased ICP versus shams (4.02±2.09), whereas blood infusion did not (5.37±0.55). The two monitoring locations gave similar readings after severe collagenase ICH. Increased ICP reduced CPP by ~7.5mmHg for days after the larger collagenase infusion. CPP averaged from 103–112mmHg in shams. Edema occurred in all ICH models and predicted ICP. However, ICP and CPP were only modestly changed even after severe ICH and edema. Thus, small changes in edema typically reported in the literature, which often use smaller bleeds than presently used, likely minimally affects ICP and CPP. Further research into the face validity of these models, endpoints, and their ability to evaluate therapeutics is needed