Delayed cerebral ischemia is a major predictor of poor outcomes in patients who suffer subarachnoid hemorrhage. Treatment options are limited and often ineffective despite many years of investigation and clinical trials. Modern advances in basic science have produced a much more complex, multifactorial framework in which delayed cerebral ischemia is better understood and novel treatments can be developed. Leveraging this knowledge to improve outcomes, however, depends on a holistic understanding of the disease process. We conducted a review of the literature to analyze the current state of investigation into delayed cerebral ischemia with emphasis on the major themes that have emerged over the past decades. Specifically, we discuss microcirculatory dysfunction, glymphatic impairment, inflammation, and neuroelectric disruption as pathological factors in addition to the canonical focus on cerebral vasospasm. This review intends to give clinicians and researchers a summary of the foundations of delayed cerebral ischemia pathophysiology while also underscoring the interactions and interdependencies between pathological factors. Through this overview, we also highlight the advances in translational studies and potential future therapeutic opportunities.

M1 and M2 cells are two major subsets of human macrophages that exert opposite effects on the inflammatory response. This study aims to investigate the role of macrophage M1/M2 imbalance and mast cells in the progression of human cerebral aneurysms to rupture. Ten patients with cerebral aneurysms (five ruptured and five unruptured) underwent microsurgical clipping. During the procedure, a segment of the aneurysm dome was resected and immunostained with monoclonal antibodies for M1 cells (anti-HLA DR), M2 cells (anti-CD 163), and mast cells (anti-tryptase clone AA). A segment of the superficial temporal artery (STA) was also removed and immunostained with monoclonal antibodies for M1, M2, and mast cells. All ten aneurysm tissues stained positive for M1, M2, and mast cells. M1 and M2 cells were present in equal proportions in unruptured aneurysms. This contrasted with a marked predominance of M1 over M2 cells in ruptured aneurysms (p = 0.045). Mast cells were also prominently upregulated in ruptured aneurysms (p = 0.001). Few M1 and M2 cells were present in STA samples. M1/M2 macrophages and mast cells are found in human cerebral aneurysms; however, M1 and mast cell expression seems to markedly increase in ruptured aneurysms. These findings suggest that macrophage M1/M2 imbalance and upregulation of mast cells may have a role in the progression of cerebral aneurysms to rupture.

Cerebral cavernous malformations are the most common vascular malformations and can be found in many locations in the brain. If left untreated, cavernomas may lead to intracerebral hemorrhage, seizures, focal neurological deficits, or headaches. As they are angiographically occult, their diagnosis relies on various MR imaging techniques, which detect different characteristics of the lesions as well as aiding in planning the surgical treatment. The clinical presentation and the location of the lesion are the most important factors involved in determining the optimal course of treatment of cavernomas. We concisely review the literature and discuss the advantages and limitations of each of the three available methods of treatment—microsurgical resection, stereotactic radiosurgery, and conservative management—depending on the lesion characteristics.

Cerebral arteriovenous malformations (AVMs) entail a significant risk of intracerebral hemorrhage owing to the direct shunting of arterial blood into the venous vasculature without the dissipation of the arterial blood pressure. The mechanisms involved in the growth, progression and rupture of AVMs are not clearly understood, but a number of studies point to inflammation as a major contributor to their pathogenesis. The upregulation of proinflammatory cytokines induces the overexpression of cell adhesion molecules in AVM endothelial cells, resulting in enhanced recruitment of leukocytes. The increased leukocyte-derived release of metalloproteinase-9 is known to damage AVM walls and lead to rupture. Inflammation is also involved in altering the AVM angioarchitecture via the upregulation of angiogenic factors that affect endothelial cell proliferation, migration and apoptosis. The effects of inflammation on AVM pathogenesis are potentiated by certain single-nucleotide polymorphisms in the genes of proinflammatory cytokines, increasing their protein levels in the AVM tissue. Furthermore, studies on metalloproteinase-9 inhibitors and on the involvement of Notch signaling in AVMs provide promising data for a potential basis for pharmacological treatment of AVMs. Potential therapeutic targets and areas requiring further investigation are highlighted.

Alterations in TNF-α expression have been associated with cerebral aneurysms, but a direct role in formation, progression, and rupture has not been established. Cerebral aneurysms were induced through hypertension and a single stereotactic injection of elastase into the basal cistern in mice. To test the role of TNF-α in aneurysm formation, aneurysms were induced in TNF-α knockout mice and mice pretreated with the synthesized TNF-α inhibitor 3,6′dithiothalidomide (DTH). To assess the role of TNF-α in aneurysm progression and rupture, DTH was started 6 days after aneurysm induction. TNF-α expression was assessed through real-time PCR and immunofluorescence staining. TNF-α knockout mice and those pre-treated with DTH had significantly decreased incidence of aneurysm formation and rupture as compared to sham mice. As compared with sham mice, TNF-α protein and mRNA expression was not significantly different in TNF-α knockout mice or those pre-treated with DTH, but was elevated in unruptured and furthermore in ruptured aneurysms. Subarachnoid hemorrhage (SAH) occurred between 7 and 21 days following aneurysm induction. To ensure aneurysm formation preceded rupture, additional mice underwent induction and sacrifice after 7 days. Seventy-five percent had aneurysm formation without evidence of SAH. Initiation of DTH treatment 6 days after aneurysm induction did not alter the incidence of aneurysm formation, but resulted in aneurysmal stabilization and a significant decrease in rupture. These data suggest a critical role of TNF-α in the formation and rupture of aneurysms in a model of cerebral aneurysm formation. Inhibitors of TNF-α could be beneficial in preventing aneurysmal progression and rupture.

The management of mycotic aneurysm has always been subject to controversy. The aim of this paper is to review the literature on the intracranial infected aneurysm from pathogenesis till management while focusing mainly on the endovascular interventions. This novel solution seems to provide additional benefits and long-term favorable outcomes.