Infections are a leading cause of death in stroke patients. In a mouse model of focal cerebral ischemia, we tested the hypothesis that a stroke-induced immunodeficiency increases the susceptibility to bacterial infections. 3 d after ischemia, all animals developed spontaneous septicemia and pneumonia. Stroke induced an extensive apoptotic loss of lymphocytes and a shift from T helper cell (Th)1 to Th2 cytokine production. Adoptive transfer of T and natural killer cells from wild-type mice, but not from interferon (IFN)-γ–deficient mice, or administration of IFN-γ at day 1 after stroke greatly decreased the bacterial burden. Importantly, the defective IFN-γ response and the occurrence of bacterial infections were prevented by blocking the sympathetic nervous system but not the hypothalamo-pituitary-adrenal axis. Furthermore, administration of the β-adrenoreceptor blocker propranolol drastically reduced mortality after stroke. These data suggest that a catecholamine-mediated defect in early lymphocyte activation is the key factor in the impaired antibacterial immune response after stroke.

The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We aim at synthesizing these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation which lead to disease.

Infections are a leading cause of morbidity and mortality in patients with acute CNS injury. It has recently become clear that CNS injury significantly increases susceptibility to infection by brain-specific mechanisms: CNS injury induces a disturbance of the normally well balanced interplay between the immune system and the CNS. As a result, CNS injury leads to secondary immunodeficiency - CNS injury-induced immunodepression (CIDS) - and infection. CIDS might serve as a model for the study of the mechanisms and mediators of brain control over immunity. More importantly, understanding CIDS will allow us to work on developing effective therapeutic strategies, with which the outcome after CNS damage by a host of diseases could be improved by eliminating a major determinant of poor recovery.

Neuroprotection and brain repair in patients after acute brain damage are still major unfulfilled medical needs. Pharmacological treatments are either ineffective or confounded by adverse effects. Consequently, endogenous mechanisms by which the brain protects itself against noxious stimuli and recovers from damage are being studied. Research on preconditioning, also known as induced tolerance, over the past decade has resulted in various promising strategies for the treatment of patients with acute brain injury. Several of these strategies are being tested in randomised clinical trials. Additionally, research into preconditioning has led to the idea of prophylactically inducing protection in patients such as those undergoing brain surgery and those with transient ischaemic attack or subarachnoid haemorrhage who are at high risk of brain injury in the near future. In this Review, we focus on the clinical issues relating to preconditioning and tolerance in the brain; specifically, we discuss the clinical situations that might benefit from such procedures. We also discuss whether preconditioning and tolerance occur naturally in the brain and assess the most promising candidate strategies that are being investigated.