Cerebrovascular diseases (CVDs) are life-threatening conditions that account for a significant percentage of global mortality (Global, 2018, Global, 2021; Krishnamurthi et al., 2020). Survivors of these disorders often experience a considerable decline in their quality of life (Duong et al., 2019). CVDs are the major cause of conditions such as ischemic and hemorrhagic stroke, including intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH), and dementia. Among these, stroke is the leading cause of death and long-term disability worldwide (Feigin et al., 2017). Annually, there are 12.2 million new cases of stroke worldwide, with a total of 101 million prevalent cases of stroke. Moreover, stroke accounts for 143 million disability-adjusted life-years and is responsible for 6.55 million fatalities (Global, 2021). The rates of mortality attributed to stroke are decreasing worldwide; however, the absolute number of patients with stroke, including deceased individuals and stroke survivors, is increasing (Feigin et al., 2014). The recent distribution of the different types of stroke is as follows: ischemic stroke, 62.4%; ICH, 27.9%; and SAH, 9.7%.(2021; Tsao et al., 2023).

Inflammation and its related responses play a pivotal role in the acute and chronic stages of the pathogenesis of these diseases. Inflammation essentially serves as a natural defensive response against various stressors, such as infections and trauma, as well as CVDs (Eming et al., 2014; Medzhitov, 2008). However, inflammation is a double-edged sword, as its effects can be divergent (Eming et al., 2017; Lambertsen et al., 2019; Scrivo et al., 2011). Inflammation can be beneficial by promoting tissue repair and clearing pathogens (LeBert and Huttenlocher, 2014). Conversely, dysregulated inflammation contributes to disease progression in patients with CVDs (Jayaraj et al., 2019; Lambertsen et al., 2019; Monsour and Borlongan, 2023; Prunell et al., 2005; Wang et al., 2023a; Wu et al., 2021; Xue and Yong, 2020; Zeyu et al., 2021). Understanding the complex phenomena underlying neuroinflammation in CVDs is important, and the scientific community is actively exploring its multifaceted role in CVDs to develop potential therapeutic strategies.

Brain immune cells, including border-associated macrophages (BAMs) and microglia, function as brain innate immunity cells and play substantial roles in inflammation. Although microglia have long been recognized as significant contributors to inflammation in the pathophysiology of CVDs, attention has recently shifted to BAMs, including perivascular macrophages (PVMs), meningeal macrophages, and choroid plexus macrophages. PVMs have been studied recently based on their significant roles in the brain. These cells are strategically positioned around the walls of brain vessels and actively participate in various vessel conditions. PVMs play a significant role in various central nervous system (CNS) diseases, including cognitive impairment (Faraco et al., 2016), Alzheimer's disease (AD) (Hawkes and McLaurin, 2009; Thanopoulou et al., 2010), multiple sclerosis (Polfliet et al., 2002; Zhang et al., 2011), viral infection (Serrats et al., 2010; Steel et al., 2010), and meningitis (Polfliet et al., 2001b). Conversely, PVMs are a potential treatment target in various CVDs based on their pleiotropic effects (Hawkes and McLaurin, 2009). Moreover, PVMs have been associated with non-CNS diseases, including myocardial infarction (Yu et al., 2010) and hypertension (Faraco et al., 2016; Iyonaga et al., 2020; Pires et al., 2013). Overall, the importance of PVMs has been increasingly recognized and highlighted, with PVMs explored as a significant pathophysiological element and a novel therapeutic target in CVDs.

This minireview provides an overview of PVMs in the context of CVD research, delving into their significant aspects and discussing potential therapeutic candidates for modulating them in CVDs. We elaborate on the characteristics, physiological roles, and mitochondrial injuries in CVDs, correlate those with PVM functions, and focus on the roles of PVMs in ischemic stroke, hemorrhagic stroke, dementia with vascular dysfunction, and clinical aspects. The understanding of the intricate interactions between PVMs and CVDs may reveal potential therapeutic targets, thereby contributing to favorable outcomes in patients with CVDs and alleviating the societal burden of these devastating conditions. As research in this field progresses and we gain deeper insights into the precise mechanisms underlying neuroinflammation, innovative therapies centered on inflammation may enhance the management and prevention of CVDs in the future. We believe that a better understanding of the roles of PVMs would provide a rationale for the development of innovative therapies for CVDs.