Molecular Biology of Brain Injury: 2012

Here we will cover a number of topics relevant to the molecular biology of acute brain injury beginning with an introduction to basic neurotransmitter systems and function, including excitatory (glutamate, acetylcholine, others) and inhibitory (GABA, glycine) neurotransmitters. To illustrate how these systems can interact with systemic processes we describe the cholinergic anti-inflammatory response, one way that the brain communicates with the peripheral immune system to downregulate an inflammatory response. Glutamate receptor physiology is introduced and the concept of excitotoxicity, central to all forms of acute central nervous system injury, is explained including the roles of metabotropic and ionotropic signaling. This leads to analysis of modes and mechanisms of programmed cell death after acute brain injury with an emphasis on programmed necrosis, apoptosis, caspases, poly-ADP-ribose polymerase, mitochondrial permeability transition, and oxidative stress, including coverage of the new field of oxidative lipidomics, which has provided a link between reactive oxygen species generation, release of mitochondrial cytochrome C, and cell death via specific oxidation of cardiolipin after acute brain and cellular injury. Links between oxidative and nitrosative stress and neuroinflammation and how these fundamental processes relate to brain injury are also included. Finally, extracellular matrix proteases, including matrix metalloproteinases and tissue plasminogen activator and their role in neurodegeneration and neuroprotection, as stroke biomarkers, and as mediators of blood–brain barrier damage are elucidated.