Immunodepression in aneurysmal subarachnoid hemorrhage patients

• Applicants: Professor Dr. Peter Martus; Dr. Christian Alexander Meisel; Professorin Dr. Asita Simone Sarrafzadeh
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology ; Immunology
• Term: from 2013 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 247490216

Aneurysmal SAH (aSAH) is a potentially devastating disorder with high mortality, aggravated by infectious complications. Trials aiming at the prevention of cerebral vasoconstriction after aSAH, failed to show an improvement in clinical outcome despite a positive drug effect on cerebral vasospasm. There might be other potential mechanisms of secondary brain injury, mainly intraparenchymal activation of the immune system contributing to delayed cerebral ischemia (DCI) after aSAH. It is hypothesized that the development of DCI is promoted by inflammatory processes leading to a decreased immunocompetence and secondarily to infectious complications. As described in a model of experimental cerebral ischemia as CNS injury-induced immunodepression syndrome (CIDS), the emergence of systemic infections after aSAH may be a symptom of disrupted immune competence. CIDS is characterised by lymphopenia, deactivation of monocytes/macrophages followed by reduced antigen-presenting capacity, secretion of pro-inflammatory cytokines and lead to systemic bacterial infections. Our preliminary data of 16 aSAH patients suggests persistent immunodepression over 10 days after aSAH only in patients with severe neurological deficits (n=9). Furthermore, immunodepression was associated with a high incidence of bacterial pneumonia. The proposed study analyzing prospectively the immune profile of SAH patients in relation to presence of ischemic deficits and occurrence of infectious complications aims to confirm the presence of immunodepression after SAH and to elucidate the cascades involved after SAH leading to delayed cerebral ischemia and infections. This approach will provide a new and sophisticated approach to boost our clinical understanding of interactions between the two supersystems, nervous and immune system and may have potential implications for prospectively identifying and treating patients at highest risk of developing DCI and infections.

• DFG Programme: Research Grants