====== Cerebral Venous Sinus Thrombosis Pathophysiology ======
The pathophysiology of CVST depends on two interconnected events, local signs due to venous infarct, e.g., hemiparesis and global signs due to raised ICP from an obstructed venous system--papilloedema and isolated intracranial hypertension being one of them. Pathophysiology of CVST is diverse and makes it easier to understand the diversity of clinical presentations
((Itrat A, Shoukat S, Kamal AK. Pathophysiology of cerebral venous
thrombosis--an overview. J Pak Med Assoc. 2006 Nov;56(11):506-8. Review. PubMed
PMID: 17183977.
)).



[[Dural venous sinus]]es are connected by channels to large [[cortical vein]]s and together make up the venous system that allows blood to drain from the cranium. [[Thrombus]] formation within a venous sinus can create a partial or complete blockage and localized congestion within the venous system and the brain; both are secondary to decreased venous outflow 

Exacerbation of venous congestion causes increased intracranial pressure, massive ischemia, and infarction of cerebral tissue. Hemorrhagic conversion can occur in larger infarctions.
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Rashad et al., from  [[Sendai]], [[Japan]] showed the intense activation of [[immune cell]]s, particularly the [[microglia]], along with the increase in [[macrophage]] activity and [[NLRP3]] [[inflammasome]] activation that is indicated by NLRP3, [[Interleukin 1 beta]] (IL-1β), and [[Interleukin 18]] gene and [[caspase 1]] [[upregulation]] and [[cleavage]] as well as [[pyroptosis]].

[[Leukocyte]]s were observed in the brain [[parenchyma]], indicating a role in [[cerebral venous thrombosis]] (CVT)-induced [[inflammation]]. In addition, [[astrocyte]]s were activated, and they induced [[glial scar]] leading to parenchymal contraction during the [[subacute]] stage and [[tissue]] loss. [[MMP9]] was responsible primarily for the [[BBB]] breakdown after CVT and it is mainly produced by [[pericyte]]s. MMP9 activation was observed before inflammatory changes, indicating that BBB breakdown is the initial driver of the pathology of CVT. These results show an inflammation driven pathophysiology of CVT that follows MMP9-mediated BBB breakdown, and identified several targets that can be targeted by pharmaceutical agents to improve the [[neuroinflammation]] that follows CVT, such as MMP9, NLRP3, and IL-1β. Some of these pharmaceutical agents are already in clinical practice or under clinical trials indicating a good potential for translating this work into patient care
((Rashad S, Niizuma K, Sato-Maeda M, Fujimura M, Mansour A, Endo H, Ikawa S,
Tominaga T. Early BBB breakdown and subacute inflammasome activation and
pyroptosis as a result of cerebral venous thrombosis. Brain Res. 2018 Jul 4. pii:
S0006-8993(18)30362-7. doi: 10.1016/j.brainres.2018.06.029. [Epub ahead of print]
PubMed PMID: 29981290.
)).