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. 2014 Apr:115:64-91.
doi: 10.1016/j.pneurobio.2013.09.002. Epub 2013 Sep 25.

Controversies and evolving new mechanisms in subarachnoid hemorrhage

Sheng Chen  1 , Hua Feng  2 , Prativa Sherchan  3 , Damon Klebe  3 , Gang Zhao  4 , Xiaochuan Sun  5 , Jianmin Zhang  6 , Jiping Tang  3 , John H Zhang  7
Affiliations

Controversies and evolving new mechanisms in subarachnoid hemorrhage

Sheng Chen et al. Prog Neurobiol. 2014 Apr.

Abstract

Despite decades of study, subarachnoid hemorrhage (SAH) continues to be a serious and significant health problem in the United States and worldwide. The mechanisms contributing to brain injury after SAH remain unclear. Traditionally, most in vivo research has heavily emphasized the basic mechanisms of SAH over the pathophysiological or morphological changes of delayed cerebral vasospasm after SAH. Unfortunately, the results of clinical trials based on this premise have mostly been disappointing, implicating some other pathophysiological factors, independent of vasospasm, as contributors to poor clinical outcomes. Delayed cerebral vasospasm is no longer the only culprit. In this review, we summarize recent data from both experimental and clinical studies of SAH and discuss the vast array of physiological dysfunctions following SAH that ultimately lead to cell death. Based on the progress in neurobiological understanding of SAH, the terms "early brain injury" and "delayed brain injury" are used according to the temporal progression of SAH-induced brain injury. Additionally, a new concept of the vasculo-neuronal-glia triad model for SAH study is highlighted and presents the challenges and opportunities of this model for future SAH applications.

Keywords: Delayed brain injury; Early brain injury; Subarachnoid hemorrhage; Vasculo-neuronal-glia triad model; Vasospasm.

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Conflict of interest statement

Conflicts of Interest: None.

Figures

Figure 1
Figure 1. Schematic of a brief SAH history
Figure 2
Figure 2. Comparison of subarachnoid hemorrhage (SAH) in human subjects and experimental endovascular perforation rat model
A, a ruptured aneurysm (red arrow) in a middle cerebral artery causes SAH in the human brain. B, a brain computed tomography (CT) scan showed a high density area in the cistern. C, SAH was produced by the endovascular filament (slim black arrow) of the internal carotid artery in a rat. D, an image of rat brain post-SAH showed a thick blood clot around the circle of Willis. E, a table summarizes the conditions of the ideal SAH model.
Figure 3
Figure 3. Mechanisms of early brain injury (EBI) and delayed brain injury (DBI) after SAH
The neurobiological responses contributing to all outcomes are listed. RBC, red blood cell; CPP, cerebral perfusion pressure; CBF, cerebral blood flow; CSD, cortical spreading depolarization; BBB, blood-brain barrier; ET-1, endothelin-1; 5-HT, 5-hydroxytryptamine; COX-2, cyclooxygenase-2; VSM, vascular smooth muscle; ENDO, endothelium.
Figure 4
Figure 4. The components of the Vasculo-Neuronal-Glia Triad Model
A. Schematic representation showing the traditional neurovascular unit as a component of the Vasculo-Neuronal-Glia triad model, which includes neurons, astrocytes, capillary endothelial cells, pericytes, smooth muscle cells, noncapillary endothelial cells, perivascular nerves, smooth muscle progenitor cells, and veins. The Vasculo-Neuronal-Glia triad model is larger than the neurovascular unit, therefore comprising all cells and structures required to maintain cerebral blood flow under physiological and pathological conditions.
Figure 5
Figure 5. Agents implicated in the connection of neurons and vessels
See this image and copyright information in PMC

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