Blood from an intracerebral hemorrhage accumulates as a mass that can dissect through and compress adjacent brain tissues, causing neuronal dysfunction. Large hematomas increase intracranial pressure. Pressure from supratentorial hematomas and the accompanying edema may cause transtentorial herniation, compressing the brainstem and often causing secondary midbrain hemorrhage and pontine hemorrhage.
If the hemorrhage ruptures into the ventricular system (intraventricular hemorrhage), blood may cause acute hydrocephalus. Cerebellar hemorrhage can expand to block the 4th ventricle, also causing acute hydrocephalus, or they can dissect into the brain stem. Cerebellar hematomas that are > 3 cm in diameter may cause midline shift or herniation.
Herniation, midbrain or pontine hemorrhage, intraventricular hemorrhage, acute hydrocephalus, or dissection into the brain stem can impair consciousness and cause coma and death.
The cause of cerebral ischemia following a hypertensive bleed was considered secondary to the compression of cerebral tissue by adjacent hematoma and oedematous tissue under raised pressure. However, studies have now found necrotic tissue in the region around the ICH, thus suggesting apoptosis caused by the expression of nuclear factor-kB within neural-cell nucleoli 1)
It is important to recognize that beyond neurons and the brain, other cell types and organs are crucially involved in ICH pathophysiology and successful interventions likely will need to address the entire organism 2).
MicroRNAs (MicroRNAs) are important regulators of translation and have been reported to be associated with the pathogenesis of numerous cerebrovascular diseases, including ICH.
A study explored the role of MicroRNA (miR)‑126 in ICH. Adult male Wistar rats were randomly assigned to ICH model and sham groups. ICH was induced by intracerebral injection of collagenase. The mRNA expression levels of miR‑126 in the two groups were determined. The miR‑126 lentivirus expression vector pWPXL‑miR‑126 or negative control vector was then constructed and delivered via intraparenchymal injection. Following transduction, behavioral testing (rotarod and limb placement tests), relative hemorrhagic lesion size, apoptotic cells and protein levels of vascular endothelial growth factor (VEGF)‑A and caspase‑3 were determined. The relative expression levels of miR‑126 were significantly decreased in the ICH group compared to the sham group (P=0.026). Overexpression of miR‑126 significantly improved the relative duration of stay on the rotarod at day 2 (P=0.029) and 3 (P=0.033), and statistically reduced the deficit score (P=0.036), the relative size of hemorrhagic lesion (P=0.019) and the number of apoptotic cortical neurons (P=0.024) compared with the sham group. Additionally, the protein levels of VEGF‑A were significantly elevated, however levels of caspase‑3 were downregulated by overexpression of miR‑126 compared with the negative control group. MiR‑126 therefore exhibits a protective role in ICH. Overexpression of miR‑126 protects against ICH, and may be involved in the process of angiogenesis and exhibit an anti-apoptotic effect 3).
Calcium is a key cofactor of the coagulation cascade and may play a role in the pathophysiology of intracerebral hemorrhage (ICH).
Hypocalcemia correlates with the extent of bleeding in patients with ICH. A low calcium level may be associated with a subtle coagulopathy predisposing to increased bleeding and might therefore be a promising therapeutic target for acute ICH treatment trials 4).
A recent increase in interest in the pathophysiology of ICH, has led to elucidation of the pathways underlying ICH-induced brain injury, pathways where intercellular and hematoma to cell signaling play important roles 5).
Increasing evidence suggests that hemoglobin and iron release from the hematoma is a major contributor to brain injury induced by ICH 6).