Effect of neurotoxic lesion of pedunculopontine nucleus in nigral and striatal redox balance and motor performance in rats.

Early degeneration of pedunculopontine nucleus (PPN) is considered part of changes that characterize premotor stages of Parkinson's disease (PD). In this paper, the effects of unilateral neurotoxic lesion of the PPN in motor execution and in the development of oxidative stress events in striatal and nigral tissues in rats were evaluated. The motor performance was assessed using the beam test (BT) and the cylinder test (CT). Nigral and striatal redox balance, was studied by means of biochemical indicators such as malondialdehyde (MDA), nitric oxide (NO) and the catalase enzymatic activity (CAT EA). Lesioned rats showed fine motor dysfunction expressed both as an increase in the length (p<0.001) and deviation (p<0.001) of the traveled path and also in the time spent (p<0.01) in the circular small beam (CBS) (p<0.01) in comparison with control groups. In addition, the lesioned rats group presented a right asymmetry index greater than 0.5 which is consistent with a significant increase in the percentage of use of the right forelimb (ipsilateral to the lesion), compared with the control group (p<0.05). Biochemical studies revealed that after 48-h PPN neurotoxic injury, the CAT EA showed a significant increase in the subtantia nigra pars compacta (SNpc) (p<0.05). This significant increase of CAT EA persisted in the nigral tissue (p<0.001) and reached the striatal tissue (p<0.001) seven days after PPN injury. Also at seven days post-injury PPN, increased concentrations of MDA (p<0.01) and a tendency to decrease in the concentrations of NO in both structures (SNpc and striatum) were found. The events associated with the generation of free radicals at nigral and striatal levels, can be part of the physiological mechanisms underlying motor dysfunction in rats with unilateral PPN neurotoxic lesion.

Quinolinic acid lesion induces changes in rat striatal glutathione metabolism.

Although the involvement of oxidative mechanisms in the cytotoxicity of excitatory amino acids has been well documented, it is not known whether the intrastriatal injection of quinolinic acid (QA) induces changes in glutathione (GSH) metabolism. In this work, the activities of the enzymes GSH reductase (GRD), GSH peroxidase (GPX), and GSH S-transferase (GST), as well as the GSH content, were studied in the striatum, hippocampus, and frontal cortex of rats 1 and 6 weeks following the intrastriatal injection of QA (225 nmol). One group of animals remained untreated. This lesion resulted in a 20% decrease in striatal GRD activity at both the 1- and 6-week postlesion times, whereas GST exhibited a 30% activity increase in the lesioned striatum observable only 6 weeks after the lesion. GPX activity remained unchanged. In addition, the QA injection elicited a 30% fall in GSH level at the 1-week postlesion time. GSH related enzyme activities and GSH content from other areas outside the lesioned striatum were not affected. GST activation could represent a beneficial compensatory response to neutralize some of the oxidant agents generated by the lesion. However, this effect together with the reduction in GRD activity could be the cause or a contributing factor to the observed QA-induced deficit in GSH availability and, consequently, further disrupt the oxidant homeostasis of the injured striatal tissue. Therefore, these results provide evidence that the in vivo excitotoxic injury to the brain might affect oxidant/antioxidant equilibrium by eliciting changes in glutathione metabolism.

[A comparative study of lesion of the fimbria-fornix by aspiration and by transsection]. / Estudio comparativo de la lesión de fimbria-fórnix por aspiración y transección.

INTRODUCTION: Lesion of the fimbria-fornix causes dysfunction of learning processes and has been used in animal models for the study of Alzheimer's disease. MATERIAL AND METHODS: With the objective of comparing the efficacy of two methods of producing a lesion of the fimbria-fornix, 40 young male Sprague-Dawley rats were distributed in four experimental groups: control (6), falsely lesioned (8), lesion due to aspiration (12) and lesion due to transection (14). RESULTS: The results showed that whilst with both techniques, in rats, serious cognitive defects were produced, as expressed by the high latencies of escape and small number of crossings of Morris's aquatic labyrinth, the aspiration lesion led to greater mortality than the transection lesion did. Similarly, the aspiration technique in rats induced hyperactivity, aggressiveness and tigmotaxia, while in the rats with lesions due to transection tigmotaxia ceased after their first attempts and hyperactivity on the second day of training. CONCLUSION: These results would suggest that a bilateral lesion due to transection of the fimbria-fornix is an effective alternative to an aspiration lesion to interrupt this pathway.

NGF prevents changes in rat brain glutathione-related enzymes following transection of the septohippocampal pathway.

The activities of the enzymes glutathione reductase (GRD), glutathione peroxidase (GPX), and glutathione S-transferase (GST) were studied in several rat brain areas following the aspirative transection of the septohippocampal pathway (fimbria fornix) and the administration of nerve growth factor (NGF) or cytochrome c. One group of animals remained untreated. This lesion resulted in a decreased hippocampal GRD and septal GST activities, as well as, in an increase in GPX activity from the frontal cortex, striatum, and septum. NGF prevented the lesion-induced changes in hippocampal GRD and septal GPX. These findings show that the insult resulting from the aspiration of the fimbria fornix bundle involves modifications in glutathione-related enzymes, and, therefore, in the antioxidant status of brain tissue. These changes in glutathione metabolism could be a consequence of the oxidative damage to GRD and GST proteins or represent a compensatory response of GPX to the oxidative threat The restoring effects of NGF on altered enzyme activities are possibly linked to its known neuroprotective action.

Estudio comparativo de la lesión de fimbria-fornix por aspiración y transección / A comparative study of lesion of thefimbria-fornix by aspiration and by transection

Introducción. La lesión de la fimbria-fornix causa disfunciones que afectan los procesos de aprendizaje y ha sido utilizada como modelo animal de enfermedad de Alzheimer. Material y métodos. Con el propósito de comparar la eficacia de dos métodos para producir la lesión de fimbria-fornix, se utilizaron 40 ratas machos jóvenes de la variedad Sprague-Dawley, distribuidas en cuatro grupos experimentales: controles (6), falsas lesionadas (8), lesionadas por aspiración (12), lesionadas por transección (14). Resultados. Los resultados mostraron que si bien ambas técnicas de lesión provocan en las ratas defectos cognitivos graves, según se expresa en las altas la

Can Cerebrolysin influence chronic deterioration of spatial learning and memory?

Our previous studies showed that the nootropic drug Cerebrolysin, applied immediately after the traumatic or excitotoxic brain lesion influenced spatial learning and memory. Long-lasting ameliorative effect of Cerebrolysin was found after its 4-week-administration, while two-week-treatment had only temporal effect. With the aim to verify the capability of Cerebrolysin to restore chronically deteriorated learning and memory. The drug was applied 4 months after lesioning the rat's CNS. The present study shows that Cerebrolysin restored learning capability of the lesioned rats. Although their spatial memory was improved in comparison to lesion untreated controls, it did not reach the level of intact controls. The effect was more pronounced after the application of 1.25 ml/kg b. w. of Cerebrolysin than after the application of 2.5 ml/kg b. w.

Can Cerebrolysin influence chronic deterioration of spatial learning and memory

Summary. Our previous studies showed that the nootropic drugs CEREBROLYSIN, applied immediately after the traumatic or excitotoxic brain lesions influenced spatial learning and memory. Long-lasting ameliorative effects of CEREBROLYSIN was found after its 4-week-administration, while 2-week-treatment had only temporal effect. With the aim to verify the capability of CEREBROLYSIN to restore chronically deterioratedlearning and memory. The drug was applied 4 months after lesioning the rat's CNS. The present study shows that CEREBROLYSIN restored learning capability of the lesioned rats. Although their spatial memory was improved in comparison to lesion untreated controls, it did not reach the level of intact controls. The effects was more pronounced after the application of 1.25 ml/kg b.w. of CEREBROLYSIN than after the application of 2.5 ml/kg b.w.(AU)

Nerve growth factor and nootropic drug Cerebrolysin but not fibroblast growth factor can reduce spatial memory impairment elicited by fimbria-fornix transection: short-term study.

In an attempt to compare effects of different neurotrophic factors on impaired memory function, young adult naive rats were trained to find the hidden platform in the Morris water maze (3 consecutive days, eight trials/day). The fimbria-fornix was unilaterally removed by aspiration and nerve growth factor (NGF) (11 micrograms/ml and 0.5 microgram/ml; groups NGF and ngf, respectively) or basic fibroblast growth factor (bFGF) (0.2 microgram/ml, group FGF) were applied via intra-cerebroventricular infusion by the osmotic minipump (flow rate 0.5 microliter/h, 14 days). Nootropic drug Cerebrolysin (EBEWE Arzneitmittel; 2.5 ml/kg/day, group CER) was applied via intraperitoneal injection (14 days). One group was formed by the rats treated with NGF (11 micrograms/ml) and Cerebrolysin (group NGFCER). Non-lesioned and lesioned only rats served as controls (groups INT and LES). After a 14-day treatment, rats were tested using the retention test (1 day, four trials). On the next day, the rats were tested using transfer test (3 days, eight trials/day). Escape latency and length of trajectory was recorded. Groups NGF, ngf, FGF and LES were similarly impaired in their ability to retrieve the old position of the platform (retention test), as well as in their ability to navigate to the new position of the platform (transfer test). In the latter, NGF group significantly differed from lesioned animals. Groups CER and NGFCER were comparable to group INT in the retention or transfer test. It is concluded that anterograde amnesia elicited by fimbria-fornix lesion can be abbreviated by NGF and/or CER, while retrograde amnesia is absent only in rats treated by CER. No short-term influence of bFGF was found. It is suggested that biochemical systems other than the cholinergic one are involved.

Study of behavior of rats with gluten-induced enteropathy

Association of different psychological and neurological disturbances with gluten intake in coeliac patients was repeatedly described. In the present study gluten-induced enteropathy was elicited in rats by prolonged intragastric administration of gliadin from birth to 10 weeks. Various neurological (contact and visual placing reactions, equilibrium on horizontal bar) and behavioral tests (open field and Morris water maze task) were used to assess the possible deficits. No substantial differences were found in the behavior of rats fed with gliadin compared with those fed with bovine serum albumin (control group). The only difference found between control and experimental rats was that gliadin-fed rats showed slightly higher emotionality in the open field test. It is concluded that prolonged application of gliadin to young rats at enteropathy-inducing dosages does not modify their behavior

Study of behavior of rats with gluten-induced enteropathy

Association of different psychological and neurological disturbances with gluten intake in coeliac patients was repeatedly described. In the present study gluten-induced enteropathy was elicited in rats by prolonged intragastric administration of gliadin from birth to 10 weeks. Various neurological (contact and visual placing reactions, equilibrium on horizontal bar) and behavioral tests (open field and Morris water maze task) were used to assess the possible deficits. No substantial differences were found in the behavior of rats fed with gliadin compared with those fed with bovine serum albumin (control group). The only difference found between control and experimental rats was that gliadin-fed rats showed slightly higher emotionality in the open field test. It is concluded that prolonged application of gliadin to young rats at enteropathy-inducing dosages does not modify their behavior (AU)

Impairment of place navigation of rats in the Morris water maxe by intermitten light is inversely related to the duration of the flash

The relative contribution of allocentric and egocentric orientation to place navigation was studied in Long-Evans rats trained in the Morris water maze in permanent light, permanent darkness or flickering light (1 Hz, flash duration 25, 100, 300, 500 and 800 ms). After 3 days of training (nine blocks of four trials), escape latencies were 38 and 7 s in the dark- and light-trained groups, respectively, and corresponded to the light-dark ratio in the flicker-trained groups. Shorter-than-predicted latencies in the 25- and 100-ms groups reflected visual persistence of 200 ms. The difference between flickerin light (100 ms) and permanent light performance during acquisition of place navigation to a new target was significantly smaller in rats previously trained in light than in naive animals. It is concluded that longer flash duration gives the animals more opportunities to locate levant landmarks and to estimate their distance

Impairment of place navigation of rats in the Morris water maxe by intermitten light is inversely related to the duration of the flash

The relative contribution of allocentric and egocentric orientation to place navigation was studied in Long-Evans rats trained in the Morris water maze in permanent light, permanent darkness or flickering light (1 Hz, flash duration 25, 100, 300, 500 and 800 ms). After 3 days of training (nine blocks of four trials), escape latencies were 38 and 7 s in the dark- and light-trained groups, respectively, and corresponded to the light-dark ratio in the flicker-trained groups. Shorter-than-predicted latencies in the 25- and 100-ms groups reflected visual persistence of 200 ms. The difference between flickerin light (100 ms) and permanent light performance during acquisition of place navigation to a new target was significantly smaller in rats previously trained in light than in naive animals. It is concluded that longer flash duration gives the animals more opportunities to locate levant landmarks and to estimate their distance (AU)