The link between carotid artery disease and ischemic stroke may be partially attributable to autonomic dysfunction and failure of cerebrovascular autoregulation triggered by Darwinian maladaptation of the carotid baroreceptors and chemoreceptors.

Carotid artery stenosis is generally thought to induce stroke by either compromising cerebral perfusion or inciting embolic phenomena. Carotid baroreceptors and chemoreceptors are vital adaptations for cerebrovascular autoregulation that can behave mal-adaptively in the setting of modern diseases such as atherosclerosis. We hypothesize that acute cerebrovascular events may be partially attributable to autonomic dysfunction and cerebrovascular autoregulatory failure secondary to carotid sensor maladaptations. Specifically, we propose that atherosclerotic disease at the carotid bifurcation can interfere with baroreceptor and chemoreceptor function by buffering against accurate detection of physical and chemical parameters. Misperceptions of hypoxia and hypotension can trigger sympathetic bias and autonomic dysfunction which perturb cerebrovascular autoregulation and vasomotor tone, thereby compromising cerebral perfusion. The preferential association of strokes with morning arousal, stress, acute physical activity, winter months, illness, and older age may relate to this phenomenon. Sympathetic bias promotes inflammation and coagulation, a link likely forged during prehistoric evolution when trauma represented a more significant factor in natural selection. In the setting of carotid sensor dysfunction, the resulting inflammation and coagulation can promote acute cardiovascular events. The ensuing cerebral ischemia can induce further derangement of cerebrovascular autoregulation and upregulate adrenergia, inflammation, and coagulation in a feed-forward manner. Inflammation and coagulation can also exacerbate carotid sensor dysfunction by iteratively worsening atherosclerosis. Angioplasty, stenting, and endarterectomy may inadvertently cause acute and chronic carotid sensor dysfunction through manipulation, material interposition, and balloon-induced baroreceptor injury. Acute strokes during these procedures may result from carotid sensor dysfunction rather than embolization. Carotid body and sinus electro-modulation and non-balloon atherectomy represent new methods to prevent or treat cerebrovascular events. Pharmacologic modulation of autonomic balance, such as adrenergic blockade, long presumed contraindicated due to risk of cerebral hypoperfusion, may counter-intuitively offer benefit during acute strokes. Novel diagnostic paradigms may include functional analysis of carotid sensors as well as measurement of the anatomic thickness of calcified and non-calcified plaque near the carotid body. Carotid sensor dysfunction may be a source of systemic sympathetic bias and autonomic dysfunction observed during aging and, by association, many of the ailments associated with senescence. Modulation of carotid sensors may yield pervasive health benefits beyond those found by treating cerebrovascular disease.

The anti-emetic action of the neurokinin(1) receptor antagonist CP-99,994 does not require the presence of the area postrema in the dog.

Microinjection and ligand binding studies have implicated NK(1) receptors in the area postrema (AP) in the emetic response to intragastric copper sulphate that is mediated by abdominal vagal afferents. Because these afferents terminate in the brainstem in the nucleus tractus solitarius in close proximity to the AP or in the AP itself, the results of such studies may be difficult to interpret. The present study has demonstrated in the dog that the emetic response to intragastric copper sulphate is unaffected by AP ablation, demonstrated functionally by absence of an emetic response to apomorphine (100 microg kg(-1) i.v.). In AP ablated animals the selective NK(1) receptor antagonist CP-99, 994 (1 mg kg(-1) i.v.) blocked the emetic response to copper sulphate as it did in intact animals. The results demonstrate that the AP is not involved in the blockade of the emetic response to intragastric copper sulphate by an NK(1) receptor antagonist and hence provides further support for other sites proposed such as the nucleus tractus solitarius and central pattern generator.

Chemosensory function and dysfunction.

Taste and smell are fundamental sensory systems essential in nutrition and food selection, for the hedonic and sensory experience of food, for efficient metabolism, and, in general, for the maintenance of a good quality of life. The gustatory and olfactory systems demonstrate a diversity of transduction mechanisms, and during the last decade, considerable progress has been made toward our understanding of the basic mechanisms of taste and smell. Understanding normal chemosensory function helps clarify the molecular events that underlie taste and smell disorders. At least 2,000,000 Americans suffer from chemosensory disorders--a number that is likely to grow as the aging segment of the population increases. Smell disorders are more frequent than taste disturbances, due to the vulnerability and anatomical distinctiveness of the olfactory system, and because a decline in olfactory function is part of the normal aging process. Common gustatory and olfactory complaints are due to a number of medications, to upper respiratory infections, to nasal and paranasal sinus diseases, and to damage to peripheral nerves supplying taste and smell. Most chemosensory complaints have an identifiable cause. Although diagnosis of taste and smell disorders has improved considerably over the last two decades, treatment of these disorders is still limited to conditions with discernible and reversible causes. Future research is needed for a better understanding of chemosensory mechanisms, establishing improved diagnostic procedures, and disseminating knowledge on chemosensory disorders among practitioners and the general public.