The neuroprotective effects of oxaloacetate in closed head injury in rats is mediated by its blood glutamate scavenging activity: evidence from the use of maleate.

INTRODUCTION: Treatment with oxaloacetate after traumatic brain injury has been shown to decrease blood glutamate levels and protect against the neurotoxic effects of glutamate on the brain. A number of potential mechanisms have been suggested to explain oxaloacetate-induced neuroprotection. We hypothesize that the primary mechanism by which intravenous oxaloacetate provides neuroprotection is by activation of the blood glutamate-scavenging enzyme glutamate-oxaloacetate transaminase, increasing thereby the driving force for the efflux of excess glutamate from brain interstitial fluids into blood. If so, coadministration of maleate, a glutamate-oxaloacetate transaminase-blocker is expected to prevent the neuroprotective effects of oxaloacetate. MATERIALS AND METHODS: A neurological severity score (NSS) was measured 1 hour after closed head injury (CHI) in rats. Then, rats received 30 microL/min/100 g infusion of saline, or 1 mmol/100 g solution of oxaloacetate, maleate, or a mixture of oxaloacetate and maleate. NSS was reassessed at 24 and 48 hour after CHI. Blood glutamate and glucose levels were measured at 0, 60, 90, and 120 minutes. RESULTS: NSS improved significantly at 24 hour (P<0.001) and 48 hour (P<0.001) only in the rats treated with oxaloacetate. Blood glutamate decreased significantly in the oxaloacetate-treated group at 90 minute (at the conclusion of oxaloacetate administration) (P<0.00001), but not in the control, maleate or oxaloacetate+maleate groups. A strong correlation r2=0.86 was found to exist between the percent decrease in blood glutamate levels and percent improvement in NSS. DISCUSSION: The results of this study demonstrate that the primary mechanism by which oxaloacetate provides neuroprotective activity after CHI is related to its blood glutamate scavenging activity. Management of blood glutamate concentration may have important implications in the treatment of acute brain conditions, including CHI and stroke.

Changes in the lens epithelium with respect to cataractogenesis: light microscopic and Scheimpflug densitometric analysis of the cataractous and the clear lens of diabetics and non-diabetics.

BACKGROUND: We compared the human lens documented, using the Scheimpflug densitometry, with the light microscopic changes in the epithelium of the anterior central lens in patients with age-related cataract and diabetes mellitus type II and verified the findings on the control tissue of the clear eye lens. We wanted to determine the relevance of the lens epithelium in cataract formation in type II diabetics compared to non-diabetics. MATERIALS AND METHODS: One hundred fifty central lens capsules (138 cataract and 12 clear lenses) of type II diabetics (n=77, 45 female, 32 male) and non-diabetics (n=73, 41 female, 32 male) were examined by light microscope, regarding defined histomorphological parameters. Further criteria were duration of diabetes, diabetic retinopathy, cataract (PENTACAM, scheimpflug densitometric definition), protein content in the aqueous humour (laser flare meter 500 KOWA, tyndallometry), different blood parameters and glucose content in the aqueous humour. RESULTS: The mean cell density in the cataractous lens in type II diabetics was 3,951+/-528 cells/mm(2) and in non-diabetics 4,329+/-580 cells/mm(2) (P<0.001); in the clear lens it corresponded to 4,593+/-409 cells/mm(2) (type II diabetics) and 4,894+/-333 cells/mm(2) (non-diabetics, P=0.207). The cell density of the cataractous lens in type II diabetics (P=0.005) and in non-diabetics (P=0.035) is smaller than that of the clear lens. The cell area of the lens epithelium in the cataractous diabetic lens is larger (P<0.001) and the nucleus-plasma ratio is lower (P<0.001) than those of the clear non-diabetic lens. The increase in damage of the lens epithelium correlates with the decrease of cell density (P< 0.001), the increase of nucleus area and volume (P< 0.001), and the decrease of nucleus-plasma ratio (P< 0.001). Risk factors for the decrease of cell density are advanced age (P=0.015), type II diabetes (P=0.01), increase in glucose content in the aqueous humour (P=0.014), increase in blood sugar (P=0.003) and increase in glycosylated haemoglobin (P=0.039). CONCLUSIONS: The lens epithelium is primarily damaged in type II diabetics who develop age-related cataract. This might play an important role in cataract formation.