Role of inflammation (leukocyte-endothelial cell interactions) in vasospasm after subarachnoid hemorrhage

Abstract 

Background

Delayed vasospasm is the leading cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). This phenomenon was first described more than 50 years ago, but only recently has the role of inflammation in this condition become better understood.

Methods

The literature was reviewed for studies on delayed vasospasm and inflammation.

Results

There is increasing evidence that inflammation and, more specifically, leukocyte-endothelial cell interactions play a critical role in the pathogenesis of vasospasm after aSAH, as well as in other conditions including meningitis and traumatic brain injury. Although earlier clinical observations and indirect experimental evidence suggested an association between inflammation and chronic vasospasm, recently direct molecular evidence demonstrates the central role of leukocyte-endothelial cell interactions in the development of chronic vasospasm. This evidence shows in both clinical and experimental studies that cell adhesion molecules (CAMs) are up-regulated in the perivasospasm period. Moreover, the use of monoclonal antibodies against these CAMs, as well as drugs that decrease the expression of CAMs, decreases vasospasm in experimental studies. It also appears that certain individuals are genetically predisposed to a severe inflammatory response after aSAH based on their haptoglobin genotype, which in turn predisposes them to develop clinically symptomatic vasospasm.

Conclusion

Based on this evidence, leukocyte-endothelial cell interactions appear to be the root cause of chronic vasospasm. This hypothesis predicts many surprising features of vasospasm and explains apparently unrelated phenomena observed in aSAH patients. Therapies aimed at preventing inflammation may prevent and/or reverse arterial narrowing in patients with aSAH and result in improved outcomes.

Abbreviations: aSAH, aneurysmal subarachnoid hemorrhage, CAM, cell adhesion molecule, CRP, C-reactive protein, CSF, cerebrospinal fluid, E-selectin, endothelial selectin, ELAM-1, endothelial leukocyte adhesion molecule, eNOS, endothelial nitric oxide synthase, ET, endothelin, GMP-140, granule membrane protein-140, Hp, haptoglobin, Hgb, hemoglobin, ICAM-1, intercellular adhesion molecule-1, IL, interleukin, JNK, c-Jun N-terminal kinase, LAM-1, leukocyte adhesion molecule-1, LECAM, leukocyte/endothelial cell adhesion molecule, L-selectin, leukocyte selectin, LFA-1, lymphocyte function-associated antigen-1, LPS, lipopolysaccharide, Mac-1, macrophage antigen-1, MEL, murine erthroleukemia, nNOS, neuronal nitric oxide synthase, NO, nitric oxide, NOS, nitric oxide synthase, NSAID, nonsteroid antiinflammatory drug, PADGEM, platelet activation dependent granule-external membrane, PARP, poly ADP-ribose polymerase, PECAM-1, platelet-endothelial cell adhesion molecule-1, P-selectin, platelet selectin, RBC, red blood cell, TCD, transcranial Doppler, TNFα, tumor necrosis factor-α, TQ, thymocyte-Q, WBC, white blood cell, VCAM-1, vascular cell adhesion molecule-1

Keywords: Endothelial cells, Haptoglobin, Hemoglobin, Inflammation, Leukocytes, Subarachnoid hemorrhage, Vasospasm