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Mechanisms of microthrombosis and microcirculatory constriction after experimental subarachnoid hemorrhage
Mohammed Sabri1, Jinglu Ai, Katarina Lakovic
1Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Abstract:
Microcirculatory dysfunction may contribute to delayed cerebral ischemia after subarachnoid hemorrhage (SAH). This study investigated structural changes in microvessels and their relationship to brain injury after SAH. We used 15 mice (n = 5 for each group) to create sham, saline-injected (100 μl 0.9% NaCl) or SAH (100 μl autologous blood) model by injection into the prechiasmatic cistern. We sacrificed mice 2 days after surgery and examined the brains using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and immunohistochemical staining of fibrinogen. We assessed neuronal apoptosis by terminal deoxynucleotidyl transferase dUTP (deoxyuridine triphosphate) nick end labeling (TUNEL). Nitric oxide (NO) was measured with 4,5-diaminofluorescein-2-diacetate. TEM and SEM demonstrated that mice with SAH had significantly more of them arterioles with lesion characteristics consistent with microthrombi. Microthrombi number correlated with the number of apoptotic neurons and decreased NO in the brain. In conclusion, SAH causes microthrombosis and constriction of arterioles, which correlates with neuronal death and decreased NO. These data suggest NO depletion may contribute to the formation of microthrombosis and arteriolar constriction, which in turn results in neuronal cell death.
Insights
Subarachnoid hemorrhage (SAH) causes microthrombosis and arteriole constriction, leading to neuronal death. This is linked to decreased nitric oxide (NO) levels, suggesting NO depletion contributes to SAH-induced brain injury.
Area of Science:
- Neuroscience
- Vascular Biology
- Pathology
Background:
- Delayed cerebral ischemia is a major complication following subarachnoid hemorrhage (SAH).
- Microcirculatory dysfunction, including microthrombosis, is implicated in SAH pathophysiology.
- Understanding microvascular changes is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate structural changes in cerebral microvessels after SAH.
- To determine the relationship between microvascular alterations and neuronal injury.
- To explore the role of nitric oxide (NO) in SAH-induced microvascular changes.
Main Methods:
- A mouse model of SAH was induced by injecting autologous blood into the prechiasmatic cistern.
- Microvascular structures were examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM).
- Neuronal apoptosis was assessed via TUNEL staining, and NO levels were measured.
Main Results:
- SAH induced significant microthrombosis and arteriolar constriction in mouse brains.
- The number of microthrombi correlated positively with neuronal apoptosis.
- Decreased nitric oxide (NO) levels were observed in SAH mice and correlated with microthrombosis.
Conclusions:
- Subarachnoid hemorrhage leads to microthrombosis and arteriolar constriction, contributing to neuronal cell death.
- Nitric oxide (NO) depletion may play a role in the development of microthrombosis and arteriolar constriction post-SAH.
- These findings highlight the critical role of microcirculatory dysfunction in SAH-induced brain injury.
