Reduction Of Cognitive Dysfunction Research Articles

Fluoride-induced alterations of synapse-related proteins in the cerebral cortex of ICR offspring mouse brain

Fluoride (F) exposure causes cognitive dysfunction in humans and animals. However, the precise molecular mechanisms by which fluoride exerts its neurotoxic effects are poorly understood. In this study, an animal model of fluoride exposure was created by providing ICR mice were treated with vehicle F at a dose of 0 (control group), 50 (low-fluoride group) or 100 mg/L (high-fluoride group) in water for one month. After the mice mated, parents and offspring were treated and maintained under these conditions. The cognitive abilities of the mice were examined using a Morris water maze test. Results indicated that fluoride exposure significantly prolonged the escape latency period and decreased the number of crossings in a particular zone. Histopathologic analysis revealed the shrinkage and fragmentation of glial cells in the fluoride-treated groups. Pyramidal cells in the cerebral cortices of fluoride-treated groups were fewer than those of the control group. The expression of microtubule-associated protein 2 (MAP2) and synaptic proteins of the cerebral cortex in mouse offspring was assayed using RT-PCR and Western blot. Fluoride exposure possibly induced a significantly decreased expression of MAP2, synaptophysin (SYP) and developmentally regulated brain protein (Dbn) at protein and mRNA levels. Glutamate receptor (N-methyl-d-aspartate receptor, NMDAR) was also expressed, and this finding was consistent with the reduced MAP2, SYP and Dbn expression. Therefore, fluoride-mediated reduction in cognitive dysfunction is likely caused by the disruption of the expression of these synapse-associated proteins, resulting in attenuated neuronal functioning.

Perispinal etanercept for post-stroke neurological and cognitive dysfunction: scientific rationale and current evidence.

There is increasing recognition of the involvement of the immune signaling molecule, tumor necrosis factor (TNF), in the pathophysiology of stroke and chronic brain dysfunction. TNF plays an important role both in modulating synaptic function and in the pathogenesis of neuropathic pain. Etanercept is a recombinant therapeutic that neutralizes pathologic levels of TNF. Brain imaging has demonstrated chronic intracerebral microglial activation and neuroinflammation following stroke and other forms of acute brain injury. Activated microglia release TNF, which mediates neurotoxicity in the stroke penumbra. Recent observational studies have reported rapid and sustained improvement in chronic post-stroke neurological and cognitive dysfunction following perispinal administration of etanercept. The biological plausibility of these results is supported by independent evidence demonstrating reduction in cognitive dysfunction, neuropathic pain, and microglial activation following the use of etanercept, as well as multiple studies reporting improvement in stroke outcome and cognitive impairment following therapeutic strategies designed to inhibit TNF. The causal association between etanercept treatment and reduction in post-stroke disability satisfy all of the Bradford Hill Criteria: strength of the association; consistency; specificity; temporality; biological gradient; biological plausibility; coherence; experimental evidence; and analogy. Recognition that chronic microglial activation and pathologic TNF concentration are targets that may be therapeutically addressed for years following stroke and other forms of acute brain injury provides an exciting new direction for research and treatment.

Neurocognitive Changes After Coronary Bypass Surgery

In this issue of Circulation , Djaiani and associates report that the processing of shed blood with a cell saver resulted in a significant reduction in postoperative neurocognitive dysfunction after coronary artery bypass surgery (CABG) in elderly patients.1 The authors further implied that this significant improvement in neurocognition was a result of less lipid embolization in those patients in whom a cell saver was used. The study was a randomized double-blinded trial that compared the use of a cell saver with cardiotomy suction (defined as control). Cardiotomy suction is a standard component of cardiopulmonary bypass (CPB), in which shed blood in the mediastinum is suctioned to a venous reservoir, where it is collected and then periodically reinfused through the arterial circuit to the patient. This technique was not used in patients in the cell saver group, but rather shed blood was suctioned via the cell saver system and processed, and red blood cells alone were infused to the patient through a similar arterial circuit. A standard 32-μm filter was used in the arterial pressure line in both groups. Article p 1888 Elderly patients who underwent CABG were chosen because it has been documented that these individuals are at increased risk to develop neurological dysfunction after cardiac surgery. The study was powered (n=209) to see a 50% reduction in cognitive dysfunction with additional patients added (for a total of 226 patients) to compensate for potential drop out, which turned out to be similar in both groups. The primary end point of neurocognitive evaluation was based on a battery of standardized and validated tests used to assess neuropsychological outcome. Evaluation was done at baseline and on follow-up at 6 weeks. In addition to neurocognitive decline, Figure 1 in Djaiani et al also demonstrates improvement in the battery of 12 tests documenting …