Recent evidence suggests a link between brain injury and the autonomic release of pro-inflammatory cytokines by resident macrophages in the spleen. This phenomenon, termed "brain-spleen inflammatory coupling," has garnered attention from scientific and medical communities interested in developing novel treatments for traumatic brain injury (TBI). Cholinergic stimulation of the α7-subunit nicotinic acetylcholine receptor (α7NAchR) on splenic macrophages has been shown to inhibit their release of pro-inflammatory cytokines. This inhibition, mediated by the parasympathetic nervous system, has been shown to improve outcomes in animal models of sepsis, stroke, and TBI. As evidence of a beneficial role of splenic inhibition grows, new treatment strategies might be applied to many medical conditions involving neuroinflammation, a process that contributes to further neurological deterioration.