Ceftriaxone pretreatment confers neuroprotection in rats with acute glaucoma and reduces the score of seizures induced by pentylenotetrazole in mice.

ß-Lactam antibiotics such as ceftriaxone, are potent stimulators of the expression of l-glutamate transporter GLT-1 and may exert neuroprotective effects when chronically used in rats and mice. In this study, we used two animal models to test the neurological effect of subchronic treatment with ceftriaxone: experimental acute glaucoma in Wistar rats and induction of acute seizures with pentylenetetrazole in mice. We also assessed the performance of mice in the rotarod to calculate therapeutic indexes and exploratory activity in the open field. Our results showed that subchronic use of ceftriaxone was neuroprotective in both models, reducing injury in acute ischemia and ischemia/reperfusion in specific layers of retina and leading to a decrease in the seizure severity score. In behavioral experiments, we observed that ceftriaxone increased hyperactivity followed by a decrease in exploratory behavior in the open field, and there was no motor impairment in the rotarod test. We conclude that ceftriaxone may be useful as a tool in the development of new neuroprotective drugs targeting diseases which present a possible dysfunction in the balance of glutamatergic neurotransmission.

The digital memory game: an assistive technology resource evaluated by children with cerebral palsy

Abstract The activities of daily living are routine self-maintenance tasks. Children with cerebral palsy can have difficulties, which can vary according to their level of motor impairment, in the performance of functional activities such as feeding and dressing themselves. The use of digital memory gaming can be a play activity and a technological resource that stimulates cognitive skills and contributes to the development of persons with disabilities. The objective of this article is to analyze the usability and effectiveness of a digital memory game for activities of daily living with children with cerebral palsy. Two children with cerebral palsy, one aged 5 and the other aged 7, participated in the investigation. The results obtained in the usability analysis are satisfactory because there were no major problems with the interface and the time available for the game and the rules presented were observed. The results also reveal the effectiveness of digital memory gaming for the recognition of objects and the activities of daily life. The importance of digital memory gaming for children with cerebral palsy is discussed. (AU)

Neuroprotective effects of oral lamotrigine administration on rabbit retinas after pars plana vitrectomy and silicone oil injection.

PURPOSE: To investigate potential retinal neuroprotective effects of oral lamotrigine in rabbits after pars plana vitrectomy (PPV) and intravitreal silicone oil injection (SOI). METHODS: Twelve New Zealand rabbits (weight, 2.0-2.5 kg) underwent PPV with SOI on the right eye. For 30 days postoperatively, 6 rabbits received a daily oral dose of lamotrigine (25 mg/kg), and 6 rabbits received a daily oral dose of water. The animals were killed 30 days after surgery. All retinas were processed histologically, immunostained using glial fibrillary acidic protein (GFAP), and analyzed by fluorescence microscopy. Retina sections from all groups were analyzed by TUNEL for the presence of apoptosis and stained with hematoxylin-eosin for morphologic analysis and retina cell density measurements in each layer using a Zeiss Axiophot microscope and KS 400 software. RESULTS: Retinas from water-operated eyes showed a significant decrease in cell density associated with cell death compared with retinas from water-control eyes; cell density was reduced by 56% in the outer nuclear layer (ONL), 49% in the inner nuclear layer (INL), and 64% in the ganglion cell layer (GCL). Lamotrigine-operated retinas showed a reduction in cell death when compared with water-operated retinas; cell death was reduced by 52% in the ONL, 25% in the INL, and 56% in the GCL. Water-operated retinas showed TUNEL-positive cells and GFAP immunofluorescence throughout Müller cell processes; lamotrigine-operated retinas showed no TUNEL-positive cells and decreased GFAP staining when compared with water-operated retinas. CONCLUSIONS: PPV with SOI was associated with apoptosis of retinal cells and activation of glial cells in rabbit eyes. Oral lamotrigine administration provided protection against these effects.

Neuroprotective effects of intramuscular ketamine in rabbit retinas after pars plana vitrectomy and silicone oil injection.

PURPOSE: To investigate potential retinal neuroprotective effects of intramuscular ketamine in rabbits after pars plana vitrectomy (PPV) and intravitreal silicone oil injection (SOI). METHODS: Twelve New Zealand rabbits (weight, 2.0-2.5 kg) underwent PPV with SOI in the right eye. Postoperatively, six rabbits received a daily intramuscular injection of ketamine for 4 weeks (ketamine-operated eyes), and six rabbits received a daily intramuscular injection of saline (saline-operated eyes). The retina from the left eye of each rabbit served as a control (ketamine-control and saline-control eyes). The animals were euthanized at 4 weeks after surgery. Qualitative and quantitative analyses were performed using the Zeiss Axiophot microscope and KS 400 software. RESULTS: Qualitative analysis using light microscopy demonstrated more extensive edema and cell disorganization in saline-operated retinas than in ketamine-operated, ketamine-control, and saline-control retinas. Quantitatively, the cell densities (cell/mm) in the outer nuclear layer (ONL), inner nuclear layer (INL), and ganglion cell layer (GCL) in saline-operated retinas were significantly (P < 0.05) lower than those in these layers in ketamine-operated, ketamine-control, and saline-control retinas. The cell density in the ONL in saline-operated retinas was 52% lower than that in ketamine-operated retinas, 55% lower than that in ketamine-control retinas, and 56% lower than that in saline-control retinas. The cell density in the INL in saline-operated retinas was 44% lower than that in ketamine-operated retinas, 48% lower than that in ketamine-control retinas, and 49% lower than that in saline-control retinas. The cell density in the GCL in saline-operated retinas was 60% lower than that in ketamine-operated retinas, 64% lower than that in ketamine-control retinas, and 64% lower than that in saline-control retinas. CONCLUSION: PPV with SOI was associated with retinal cell death and disorganization in rabbit eyes. Intramuscular ketamine administration provided protection against these effects.

The biological activity in mammals and insects of the nucleosidic fraction from the spider Parawixia bistriata.

Previous work has shown that the crude venom of Parawixia bistriata induces convulsive seizures in rats after intracerebroventricular injection. In this work, the isolation of a bioactive fraction with ultraviolet absorption characteristics of nucleic acid and trace protein or amino acid content is described. NMR analysis demonstrated that the major component of the active fraction is the nucleoside inosine. An analogue of this component (inosine 5'-monophosphate) induced a delayed paralysis effect in termites.

Purification of a neuroprotective component of Parawixia bistriata spider venom that enhances glutamate uptake.

(1) In this study, we examined the effects of crude venom from the spider Parawixia bistriata on glutamate and GABA uptake into synaptosomes prepared from rat cerebral cortex. Addition of venom to cortical synaptosomes stimulated glutamate uptake and inhibited GABA uptake in a concentration-dependent manner. (2) The venom was fractionated using reverse-phase high-performance liquid chromatography on a preparative column. The fraction that retained glutamate uptake-stimulating activity was further purified on a reverse-phase analytical column followed by ion-exchange chromatography. (3) The active fraction, referred to as PbTx1.2.3, stimulated glutamate uptake in synaptosomes without changing the K(M) value, and did not affect GABA uptake. Additional experiments showed that the enhancement of glutamate uptake by PbTx1.2.3 occurs when ionotropic glutamate receptors or voltage-gated sodium and calcium channels are completely inhibited or when GABA receptors and potassium channels are activated, indicating that the compound may have a direct action on the transporters. (4) In an experimental model for glaucoma in which rat retinas are subjected to ischemia followed by reperfusion, PbTx1.2.3 protected neurons from excitotoxic death in both outer and inner nuclear layers, and ganglion cell layers. (5) This active spider venom component may serve as a basis for designing therapeutic drugs that increase glutamate clearance and limit neurodegeneration.