Neuropathological features of cerebrovascular diseases

Optimal blood flow through a patent cerebral circulation is critical for supply of oxygen and nutrients for brain function. The integrity of vascular elements within arterial vessels of any calibre can be compromised by various disease processes. Pathological changes in the walls of veins and the venous system may also alter the dynamics of cerebral perfusion. The consequences of both systemic vascular and cerebrovascular diseases range from acute focal changes to irreversible chronic restructuring of the brain parenchyma. Cerebral infarcts of different sizes may instigate a cascade of programmed cell death mechanisms including autophagy and mitophagy and processes that range from necroptosis to ferroptosis. Recent advances also emphasise the role of the vascular inflammasome in the pathology of cerebral infarction. Here, we summarise current knowledge on frequencies, epidemiological features and the neuropathology of common cerebrovascular disorders among which cerebral small vessel diseases have become of particular interest. We also highlight the current spectrum of monogenic and polygenic genetic disorders affecting the intracranial vasculature. With the advent of DNA screening technologies, it is now realised that several cerebrovascular disorders exhibit strong genetic traits. Whilst several gene defects and their aberrant products are identified, the precise role or mechanisms of how they influence angiogenesis, vasculogenesis, vessel integrity or the extracellular matrix remain largely unclear. Despite such genetic advances, histopathological examination remains the gold standard for diagnosis and characterisation of most cerebrovascular disorders.