A Nuclear Microscopic Study of Elemental Changes in the Rat Hippocampus After Kainate‐Induced Neuronal Injury

Abstract

Abstract:The effect of intracerebroventricular kainate injection on the elemental composition of the hippocampus was studied in adult Wistar rats, at 1 day and 1, 2, 3, and 4 weeks postinjection, using a nuclear microscope. An increase in calcium concentration was observed on the injected side from 1 day postinjection. The increase peaked at 3 weeks postinjection, reaching a concentration of 18 times normal. Large numbers of glial cells but no neurons were observed in the lesioned CA fields at this time, suggesting that an increased calcium level was present in glial cells. This was confirmed by high-resolution elemental maps of the lesioned areas, which showed very high intracellular calcium concentrations in almost all glial cells. It is possible that the high intracellular calcium level could activate calcium-dependent enzymes, including calpain II and cytosolic phospholipase A 2 , shown to be expressed in reactive glial cells after kainate injections. In addition to calcium, an increase in iron content was also observed at the periphery of the glial scar at 4 weeks postinjection. Because free iron could catalyze the formation of free radicals, the late increase in iron content may be related to oxygen radical formation during neurodegeneration.

Inhibitors of Brain Phospholipase A2Activity: Their Neuropharmacological Effects and Therapeutic Importance for the Treatment of Neurologic Disorders

“…These mechanisms not only include inhibition of mitochondrial function and increases in intracellular calcium ion, due to depolarization, but also free radical generation ). Our nuclear microscopic studies have clearly indicated a steady increase in calcium ion at 1, 2, and 3 weeks after KA injection (Ong et al, 1999). This increase in calcium ion may be responsible for the stimulation of many calcium-dependent enzymes including isoforms of PLA 2 (Sandhya et al, 1998), calpain II (Ong et al, 1997), and endonucleases during KA-induced neurotoxicity.…”

Slow Excitotoxicity in Alzheimer's Disease

“…Iron may promote the formation of free radicals by A␤, via the methionine 35 residue of A␤ [240]. A late increase in iron level is detected in the degenerating hippocampus after KA induced excitotoxicity, using the quantitative method of nuclear microscopy [241]. In addition, there is a shift in the oxidation state of iron, with more cells becoming positive for ferrous iron at a later time (months).…”

Comparison of in vivo binding properties of the 18-kDa translocator protein (TSPO) ligands [18F]PBR102 and [18F]PBR111 in a model of excitotoxin-induced neuroinflammation

“…The validity of μ-PIXE for quantitative measurement of Ca concentration/maps has been shown previously in animal models in which excitotoxicity is a fundamental process, such as brain ischaemia, where time-dependent increases in key brain structures are seen [38]. Likewise, in the kainic acid model of epilepsy, site-specific Ca ion increases were seen in key epileptogenic brain regions during the asymptomatic phase of the disease up to 4 weeks after disease initiation [39]. On the basis of our μ-PIXE results, it would appear that the 7-day time-point would still be a valid time-point for assessing the effects of therapeutic interventions in neuroinflammation, increasing the utility of this model.…”