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. 2023 Apr 25;24(9):7832.
doi: 10.3390/ijms24097832.

Compartmental Cerebrospinal Fluid Events Occurring after Subarachnoid Hemorrhage: An "Heparin Oriented" Systematic Review

Fulvio Tartara  1 , Andrea Montalbetti  2 , Emanuela Crobeddu  2 , Daniele Armocida  3   4 , Eleonora Tavazzi  1 , Andrea Cardia  5 , Marco Cenzato  6 , Davide Boeris  6 , Diego Garbossa  7 , Fabio Cofano  7
Affiliations

Compartmental Cerebrospinal Fluid Events Occurring after Subarachnoid Hemorrhage: An "Heparin Oriented" Systematic Review

Fulvio Tartara et al. Int J Mol Sci. .

Abstract

Subarachnoid hemorrhage (SAH) represents a severe acute event with high morbidity and mortality due to the development of early brain injury (EBI), secondary delayed cerebral ischemia (DCI), and shunt-related hydrocephalus. Secondary events (SSE) such as neuroinflammation, vasospasm, excitotoxicity, blood-brain barrier disruption, oxidative cascade, and neuronal apoptosis are related to DCI. Despite improvement in management strategies and therapeutic protocols, surviving patients frequently present neurological deficits with neurocognitive impairment. The aim of this paper is to offer to clinicians a practical review of the actually documented pathophysiological events following subarachnoid hemorrhage. To reach our goal we performed a literature review analyzing reported studies regarding the mediators involved in the pathophysiological events following SAH occurring in the cerebrospinal fluid (CSF) (hemoglobin degradation products, platelets, complement, cytokines, chemokines, leucocytes, endothelin-1, NO-synthase, osteopontin, matricellular proteins, blood-brain barrier disruption, microglia polarization). The cascade of pathophysiological events secondary to SAH is very complex and involves several interconnected, but also distinct pathways. The identification of single therapeutical targets or specific pharmacological agents may be a limited strategy able to block only selective pathophysiological paths, but not the global evolution of SAH-related events. We report furthermore on the role of heparin in SAH management and discuss the rationale for use of intrathecal heparin as a pleiotropic therapeutical agent. The combination of the anticoagulant effect and the ability to interfere with SSE theoretically make heparin a very interesting molecule for SAH management.

Keywords: blood brain barrier; cytokines; delayed cerebral ischemia; heparin; neuroinflammation; subarachnoid hemorrhage; vasospasm.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The PRISMA 2020 flow diagram for systematic reviews of “Compartmental cerebrospinal fluid events occurring after subarachnoid hemorrhage” [17].
Figure 2
Figure 2
Schematic representation of pathophysiological events occurring in the subarachnoid compartment after SAH.
Figure 3
Figure 3
Diagram summarizing the potential effect of heparin on post-SAH pathophysiological events.
See this image and copyright information in PMC

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