Evidence for Decreased Brain Parenchymal Volume After Large Intracerebral Hemorrhages: a Potential Mechanism Limiting Intracranial Pressure Rises

Abstract

Potentially fatal intracranial pressure (ICP) rises commonly occur after large intracerebral hemorrhages (ICH). We monitored ICP after infusing 100–160 μL of autologous blood (vs. 0 μL control) into the striatum of rats in order to test the validity of this common model with regard to ICP elevations. Other endpoints included body temperature, behavioral impairment, lesion volume, and edema. Also, we evaluated hippocampal CA1 sector and somatosensory cortical neuron morphology to assess whether global ischemic injury occurred. Despite massive blood infusions, ICP only modestly increased (160 μL 10.8 ± 2.1 mmHg for <36 h vs. control 3.4 ± 0.5 mmHg), with little peri-hematoma edema at 3 days. Body temperature was not affected. Behavioral deficits and tissue loss were infusion volume-dependent. There was no histological evidence of hippocampal or cortical injury, indicating that cell death was confined to the hematoma and closely surrounding tissue. Surprisingly, the most severe hemorrhages significantly increased cell density (~15–20%) and reduced cell body size (~30%) in regions outside the injury site. Additionally, decreased cell size and increased density were observed after collagenase-induced ICH. Parenchymal volume is seemingly reduced after large ICH. Thus, in addition to well-known compliance mechanisms (e.g., displacement of cerebrospinal fluid and cerebral blood), reduced brain parenchymal volume appears to limit ICP rises in rodents with very large mass lesions.

Failure of bumetanide to improve outcome after intracerebral hemorrhage in rat

“…Samples of abdominal muscle and thigh muscle were taken immediately following euthanasia. Muscle water content was determined using the wet weight-dry weight method and used as an additional measure of hydration [35].…”

“…Brain water content was measured using the wet weight-dry weight method (baking at 100°C for 24 hr) at 48 hours post-ICH [35]. Tissue samples were taken 2 mm anterior until 4 mm posterior to the infusion site and separated into cortical and striatal tissue.…”

Simvastatin Reduces Neutrophils Infiltration Into Brain Parenchyma After Intracerebral Hemorrhage via Regulating Peripheral Neutrophils Apoptosis

“…Tissue water content was calculated as (wet weight – dry weight)/wet weight. The brain water content was measured by as previously described (Williamson and Colbourne, 2017).…”

An Update On Medical Treatment for Intracerebral Hemorrhage

“…At the onset of ICH, within the first few hours, the bleeding leads to the formation of hematoma and mechanical damage to adjacent tissues, which results in a sharp increase in intracranial pressure and induces primary brain injury [4]. At present, surgical operation is adopted to remove hematoma and reduce the intracranial pressure [5]. The Surgical Trail in Intracerebral Hemorrhage (STICH) has failed to provide positive evidence to support the effect of surgical operation, and STICH2 also showed no benefit (NCT01320423) [6,7].…”

“…), chemokines, adhesion molecular, matrix metalloproteinase (MMP, MMP9 and MMP3), and cell death products, which could disrupt BBB and destroy surrounding tissues [2,26,[50][51][52][53][54][55][56][57]. Therefore, brain inflammation has become a critical modifiable determinant target for the development of ICH-induced SBI treatment [5,58]. Due to the mitigation of inflammation, celecoxib, a cyclooxygenase-2 inhibitor, has been investigated in the ICH pilot clinical trial (NCT00526214) [59].…”