The social cognition of medical knowledge, with special reference to childhood epilepsy

This paper arose out of an engagement in medical communication courses at a Gulf university. It deploys a theoretical framework derived from a (critical) sociocognitive approach to discourse analysis in order to investigate three aspects of medical discourse relating to childhood epilepsy: the cognitive processes that are entailed in relating different types of medical knowledge to their communicative context; the types of medical knowledge that are constituted in the three different text types analysed; and the relationship between these different types of medical knowledge and the discursive features of each text type. The paper argues that there is a cognitive dimension to the human experience of understanding and talking about one specialized from of medical knowledge. It recommends that texts be studied in medical communication courses not just in terms of their discrete formal features but also critically, in terms of the knowledge which they produce, transmit and reproduce

Obesity-induced cognitive impairment in older adults: a microvascular perspective

Over two-thirds of individuals aged 65 and older are obese or overweight in the United States. Epidemiological data show an association between the degree of adiposity and cognitive dysfunction in the elderly. In this review, the pathophysiological roles of microvascular mechanisms, including impaired endothelial function and neurovascular coupling responses, microvascular rarefaction, and blood-brain barrier disruption in the genesis of cognitive impairment in geriatric obesity are considered. The potential contribution of adipose-derived factors and fundamental cellular and molecular mechanisms of senescence to exacerbated obesity-induced cerebromicrovascular impairment and cognitive decline in aging are discussed

The modified 2VO ischemia protocol causes cognitive impairment similar to that induced by the standard method, but with a better survival rate

Permanent bilateral occlusion of the common carotid arteries (2VO) in the rat has been established as a valid experimental model to investigate the effects of chronic cerebral hypoperfusion on cognitive function and neurodegenerative processes. Our aim was to compare the cognitive and morphological outcomes following the standard 2VO procedure, in which there is concomitant artery ligation, with those of a modified protocol, with a 1-week interval between artery occlusions to avoid an abrupt reduction of cerebral blood flow, as assessed by animal performance in the water maze and damage extension to the hippocampus and striatum. Male Wistar rats (N = 47) aged 3 months were subjected to chronic hypoperfusion by permanent bilateral ligation of the common carotid arteries using either the standard or the modified protocol, with the right carotid being the first to be occluded. Three months after the surgical procedure, rat performance in the water maze was assessed to investigate long-term effects on spatial learning and memory and their brains were processed in order to estimate hippocampal volume and striatal area. Both groups of hypoperfused rats showed deficits in reference (F(8,172) = 7.0951, P < 0.00001) and working spatial memory [2nd (F(2,44) = 7.6884, P < 0.001), 3rd (F(2,44) = 21.481, P < 0.00001) and 4th trials (F(2,44) = 28.620, P < 0.0001)]; however, no evidence of tissue atrophy was found in the brain structures studied. Despite similar behavioral and morphological outcomes, the rats submitted to the modified protocol showed a significant increase in survival rate, during the 3 months of the experiment (P < 0.02)

Diazoxide and dimethyl sulphoxide alleviate experimental cerebral hypoperfusion-induced white matter injury in the rat brain

Aging and dementia are accompanied by cerebral white matter (WM) injury. which is considered to be of ischemic origin. A causal link between cerebral ischemia and WM damage has been demonstrated in rats: however. few attempts appear to have, been made to test potential drugs for the alleviation of ischemia-related WM injury. We induced cerebral hypoperfusion via permanent, bilateral occlusion of the common carotid arteries of rats. A mitochondrial ATP-sensitive potassium channel opener diazoxide (5 or its solvent dimethyl sulphoxide (DMSO) was administered i.p. (0.25 ml) on 5 consecutive. days after surgery. Sham-operated animals served as control for surgery. and non-treated rats as controls for treatments. Thirteen weeks after surgery, the animals were sacrificed and astrocytes and microglia were labeled immunocytochemically in the internal capsule, the corpus callosum and the optic tract. The astrocytic proliferation was enhanced by cerebral hypoperfusion in the optic tract, and reduced by diazoxide in DMSO. but not by DMSO alone in the corpus callosum. After carotid artery occlusion, microglial activation was enhanced two-fold in the corpus callosum and four-fold in the optic tract. DMSO decreased microglial activation in the optic tract, while diazoxide in DMSO. but not DMSO alone.. restored microglial activation to the control level in the corpus callosum. In summary, the rat optic tract appeared to be particularly vulnerable to ischemia. while the effect of diazoxide was restricted to the corpus callosum. We conclude that diazoxide dissolved in DMSO can moderate ischemia-related neuroinflammation by suppressing glial reaction in selective cerebral WM areas. (C) 2004 Elsevier Ireland Ltd. All rights reserved

Abstract 3903: Dynamin-related Protein 1 Independent Apoptosis In Neurons Following Oxygen-glucose Deprivation

Background and purpose: Previous studies showed that mitochondrial (mito) fission occurs prior to apoptosis and that a key initiator is the mito fission protein dynamin-related protein 1 (Drp1). However, little information is available concerning mito dynamics in neurons due to OGD. Therefore, we investigated mito fission and mito fusion responses in cultured neurons in an in vitro model of brain ischemia. Methods: Primary rat cortical neurons were isolated from E18 Sprague Dawley fetuses. Neurons were exposed to OGD 9 days after culturing for 3 hr followed by up to 24 hr of reoxygenation. Mito dynamics were investigated by measuring the expression of: 1) mito fission [Drp1; mito fission 1 (Fis1)] and mito fusion [mitofusin-2 (Mfn2); optic atrophy-1 (OPA1)] proteins; 2) electron transport chain proteins (complex II 70 kDa subunit, complex IV subunit I, complex V alpha subunit); 3) mito DNA; and 4) apoptosis protein Bax. We also examined neuronal and mito morphology using transmission electron microscopy. The effects of the Drp1 inhibitors 15d-Prostaglandin J 2 (2.5-20 µM) (15d-PGJ 2 ) and Mdivi-1 (2.5-250 µM) were also investigated. Results: 3hr OGD followed by 3-24 hr recovery resulted in an increase in the level of mito DNA and enhanced expression of complex IV and V proteins. During this time, abnormal morphology, including enlarged and/or swollen mitochondria, was often observed. However, many mitochondria still retained normal morphology. Drp1 levels decreased before virtually disappearing by 6 hr of reoxygenation following OGD while Fis1 expression did not change. Bax expression increased with an increasing number of apoptotic cells during this time. Mfn2 decreased after OGD while OPA1 did not change significantly. 15d-PGJ 2 treatment dose-dependently increased cell death both in control and OGD-exposed neurons. Furthermore, 15d-PGJ 2 treatment surprisingly increased Drp1 both in controls and in OGD-exposed cells, and also increased the mito DNA. Additionally, 15d-PGJ 2 treatment itself increased the number of larger mitochondria in the neurons. However, Mdivi-1 did not have any effects. Conclusions: Despite a lower fission/fusion protein ratio, the increase in mitochondrial size indicates a shift to enhanced fusion in neurons following OGD. In addition, apoptosis induction seems to be Drp1 independent in this model. Additionally, 15d-PGJ 2 treatment appears to decrease survival in neurons following OGD. Thus, mito dynamics are affected by OGD and 15d-PGJ 2 treatment and play a role in cell survival/death. </jats:p

Mitochondrial dynamics associated with oxygen-glucose deprivation in rat primary neuronal cultures.

Our objective was to investigate the mitochondrial dynamics following oxygen-glucose deprivation (OGD) in cultured rat cortical neurons. We documented changes in morphology, protein expression, and DNA levels in mitochondria following OGD and examined the roles of mitochondrial fission [dynamin-related protein 1 (Drp1), fission protein-1 (Fis1)] and fusion [mitofusin-1 (Mfn1), mitofusin-2 (Mfn2), and optic atrophy-1 protein (OPA1)] proteins on mitochondrial biogenesis and morphogenesis. We tested the effects of two Drp1 blockers [15-deoxy-Δ12,14-Prostaglandin J2 (PGJ2) and Mitochondrial Division Inhibitor (Mdivi-1)] on mitochondrial dynamics and cell survival. One hour of OGD had minimal effects on neuronal viability but mitochondria appeared condensed. Three hours of OGD caused a 60% decrease in neuronal viability accompanied by a transition from primarily normal/tubular and lesser number of rounded mitochondria during normoxia to either poorly labeled or small and large rounded mitochondria. The percentage of rounded mitochondria remained the same. The mitochondrial voltage-dependent anion channel, Complex V, and mitoDNA levels increased after OGD associated with a dramatic reduction in Drp1 expression, less reduction in Mfn2 expression, an increase in Mfn1 expression, with no changes in either OPA1 or Fis1. Although PGJ2 increased polymerization of Drp1, it did not reduce cell death or alter mitochondrial morphology following OGD and Mdivi-1 did not protect neurons against OGD. In summary, mitochondrial biogenesis and maintained fusion occurred in neurons along with mitochondrial fission following OGD; thus Mfn1 but not Drp1 may be a major regulator of these processes