Cold shock protects the brain

Abstract

A protein released during hypothermia has been found to affect the progression of neurodegenerative disease in mice by sparing neurons from death and preserving the connections between them. History is littered with examples of the use of cold as a therapeutic agent — from the ancient Greek physician Claudius Galen, who used it to treat fevers, to its application for improving the outcomes of surgery after serious battlefield injuries. Mounting evidence of its effectiveness led surgeons in the 1950s to use hypothermia as a tool to ameliorate the side effects of brain surgery1, and even today, cold is an effective treatment for birth asphyxia — a lack of oxygen during the perinatal period that can lead to brain damage. It was not until 1987 that an animal study2 showed that cooling could reduce neuronal death after brain injury. In a paper published on Nature's website today, Peretti et al.3 provide compelling evidence that a specific protein affects the brain's ability to reshape its connections in response to cooling, and that the protein's overexpression might provide therapeutic benefits in neurodegenerative disease. The neuroprotection offered by cold has spurred efforts to understand the mechanisms responsible, and findings so far offer insight into how brain metabolism and cell death are affected4. One aspect of neuroprotection research that is attracting interest involves a small group of proteins whose synthesis increases during hypothermia, even as production of other proteins decreases. These cold-shock proteins, which are found in many species, bind with RNA and mediate overall protein production. One such protein in particular, RNA-binding motif protein 3 (RBM3), is emerging as a central player in the protection of neurons after periods of hypothermia5. Investigations have focused mainly on how RBM3 and other cold-shock proteins affect the outcome of various types of stroke.