RESUMO
Development of manganism (also known as manganese neurotoxicity) is a major complication of manganese exposure in which neurological dysfunction is linked to accumulation of the metal in brain. Due to neuronal cell death in basal ganglia structures, particularly the globus pallidus, functional recovery is limited. Bearing a resemblance to Parkinson's disease, effective treatment for manganism is currently limited. However, the rapidly developing field of stem cell research offers new hope for the treatment of illnesses in which neurodegeneration is a major feature. The first part of this review will focus on the clinical features and pathophysiology of cerebral damage resulting from exposure to manganese, including the role of astrocytes, disruption of energy metabolism, involvement of oxidative stress, excitotoxicity, and inflammation, with the second part exploring how stem cells may provide an important therapeutic strategy for patients with this major neurologic disorder.
Assuntos
Intoxicação por Manganês/terapia , Estresse Oxidativo/fisiologia , Transplante de Células-Tronco/métodos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Humanos , Intoxicação por Manganês/metabolismo , Transplante de Células-Tronco/tendências , Resultado do TratamentoRESUMO
Thiamine deficiency (TD) is the underlying cause of Wernicke's encephalopathy (WE), an acute neurological disorder characterized by structural damage to key periventricular structures in the brain. Increasing evidence suggests these focal histological lesions may be representative of a gliopathy in which astrocyte-related changes are a major feature of the disorder. These changes include a loss of the glutamate transporters GLT-1 and GLAST concomitant with elevated interstitial glutamate levels, lowered brain pH associated with increased lactate production, decreased levels of GFAP, reduction in the levels of glutamine synthetase, swelling, alterations in levels of aquaporin-4, and disruption of the blood-brain barrier. This review focusses on how these manifestations contribute to the pathophysiology of TD and possibly WE.