Daniel Lavinsky

Agmatine induces anxiolysis in the elevated plus maze task in adult rats

Agmatine is an endogenous released polyamine recently proposed to be a putative neurotransmitter, however its physiological role is still to be determined. We investigated the hypothesis that agmatine, systemically administered to adult Wistar rats, might exert anxiolytic-like behavior in the elevated plus maze (EPM) and the open field. Agmatine (1, 10, 20, 40 and 100 mg/kg) and saline were administered i.p. 30 min before the EPM and the open field. Administration of agmatine (20 and 40 mg/kg) increased the time spent in the open arms of the EPM, as compared to the saline group, with no effect on locomotion activity in the open field. However, 100 mg/kg of agmatine significantly reduced the number of entries into enclosed arms of the EPM and the total number of crossings in the open field. We suggest that agmatine, in doses of 20 and 40 mg/kg, causes a mild anxiolytic-like behavior and discuss the possibility that this first reported effect could be caused either by the inhibition of nitric oxide synthase, the blockage of NMDA receptors or by the activation of alpha-2-adrenoceptors.

Lateralized and sex-dependent behavioral and morphological effects of unilateral neonatal cerebral hypoxia-ischemia in the rat

Neonatal cerebral hypoxia-ischemia (HI) is an important cause of neurological deficits. The Levine-Rice model of unilateral HI is a useful experimental tool, but the resulting brain damage is mainly restricted to one hemisphere. Since the rat presents morphological and biochemical asymmetries between brain hemispheres, behavioral outcome from this model is probably dependent on which hemisphere is damaged. We here investigated the effects of sex and lesioned hemisphere on the outcome of open field, plus maze, inhibitory avoidance and water maze tasks in adult rats previously submitted to neonatal unilateral HI. Females were more active than males in some of studied parameters and males presented better spatial learning. Hypoxia-ischemia caused spatial deficits independently of sex or damaged hemisphere. Right-HI increased locomotion only in males and caused working memory in females and on aversive learning in both males and females. Morphological analysis showed that right-HI animals presented greater reduction of ipsilateral striatum area, with females being more affected. Interestingly, males showed greater hippocampal volume. These results show that task performance and cerebral damage extension are lateralized and sex-dependent, and that the right hemisphere, irrespective of sex, is more vulnerable to neonatal cerebral hypoxia-ischemia.

Hypoxic-ischemic insult decreases glutamate uptake by hippocampal slices from neonatal rats: Prevention by guanosine

Brain injury secondary to hypoxic-ischemic disease is the predominant form of damage encountered in the perinatal period. The impact of neonatal hypoxia-ischemia (HI) in 7-day-old pups on the high-affinity [3H] glutamate uptake into hippocampal slices at different times after insult was examined. Immediately following, and 1 day after the insult there was no effect. But at 3 to 5 days after the HI insult, glutamate uptake into the hippocampus was markedly reduced; however, after 30 or 60 days the glutamate uptake into hippocampal slices returned to control levels. Also, this study demonstrated the effect of the nucleoside guanosine (Guo) on the [3H] glutamate uptake in neonatal HI injury, maintaining the [3H] glutamate uptake at control levels when injected before and after insult HI. We conclude that neonatal HI influences glutamate uptake a few days following insult, and that guanosine prevents this action.

Agmatine facilitates memory of an inhibitory avoidance task in adult rats.

Agmatine is a new putative neurotransmitter; however, the physiological role(s) of this endogenous released polyamine is still to be determined. We investigated its cognitive effect in an inhibitory avoidance task in adult rats. Agmatine (0.1, 1, 10, and 20 mg/kg) or saline was administered ip immediately after training or 1 h before testing. Posttraining injection of agmatine facilitated (p < 0.05) memory consolidation in this task; however pretest treatment showed no effect on retrieval (p > 0.05). We suggest that the facilitatory effect of agmatine on memory consolidation in inhibitory avoidance task might be mediated through the activation of the locus coeruleus.

Chronic bilateral common carotid artery occlusion: a model for ocular ischemic syndrome in the rat

BackgroundOcular ischemic syndrome is a devastating eye disease caused by severe carotid artery stenosis. The reduction of blood flow produced by bilateral common carotid artery occlusion (BCCAO) of rats for 7 days induces events related to gliosis with no evident histological damage. However, retinal degeneration and cellular death occur after 90 days of BCCAO. Our purpose has been to investigate the effects of BCCAO for 30 days in the retina of adult rats.MethodsAdult Wistar rats were submitted to BCCAO or sham surgery. Both direct and consensual pupillary light reflexes were investigated before and after surgery, everyday for the first week and weekly for 30 days. After 1 month, eyes were enucleated and embedded in paraffin. The retinal ganglion cell (RGC) density and thickness of the internal plexiform (IPL), internal nuclear, outer plexiform, and outer nuclear layers were estimated.ResultsFour rats of the BCCAO group (50%) lost the direct pupillary reflex in both eyes, three rats (37%) lost this reflex in one eye, and only one (13%) maintained it in both eyes. RGC density (cells/mm) was diminished in the BCCAO group, and a significant decrease was found in the total retina and IPL thickness; however, no changes were evident in the other layers. BCCAO pupillary-reflex-negative rats presented with a significant decrease in total retinal thickness and retinal ganglion cell density compared with the sham group. Both BCCAO pupillary-reflex-positive) and -negative rats showed a decrease in IPL compared with the sham group.ConclusionThis study demonstrates that BCCAO for 30 days induces functional and morphological damage to the retina with loss of the pupillary reflex and a decrease in IPL thickness and RGC number. We suggest that this protocol might be used as a model for ocular ischemic syndrome in the rat.

Neonatal hypoxia-ischemia reduces ganglioside, phospholipid and cholesterol contents in the rat hippocampus

Hypoxia-ischemia is a common cause of neonatal brain damage producing serious impact on cerebral maturation. This report demonstrates that rats submitted to hypoxia-ischemia present a marked decrease in hippocampal gangliosides, phospholipids and cholesterol contents as from 7 days after the injury. Although chromatographic profiles of the different ganglioside species (GM1, GD1a, GD1b, and GT1b) from the hippocampus of hypoxic-ischemic hippocampi groups (HI) were apparently unaffected, as compared with controls, there were quantitative absolute reductions in HI. The phospholipid patterns were altered in HI as from the 14th to the 30th day after the injury, where phosphatidylcholine (PC) quantities were higher than phosphatidylethanolamine (PE); additionally, the cardiolipin band was detected only in hippocampi of control adult rats. In general, the absolute quantities of phospholipids were lower in HI than in correspondent controls since 7th day after the injury. Considering that reported effects were maintained, we suggest they express a late biochemical response triggered by the neonatal hypoxic-ischemic episode; the consequences would be cell death and a delay on brain development, expressed by a reduction on synaptogenesis and myelinogenesis processes.

Importance of Schedule of Administration in the Therapeutic Efficacy of Guanosine: Early Intervention After Injury Enhances Glutamate Uptake in Model of Hypoxia-ischemia

Perinatal cerebral hypoxia–ischemia (HI) is an important cause of mortality and neurological disabilities such as cerebral palsy, epilepsy, and mental retardation. The potential for neuroprotection in HI can be achieved mainly during the recovery period. In previous work, we demonstrated that guanosine (Guo) prevented the decrease of glutamate uptake by hippocampal slices of neonatal rats exposed to a hypoxic-ischemic (HI) insult in vivo when administrated before and after insult. In the present study, we compared the effect of Guo administration only after HI using various protocols. When compared with the control, a decrease of [3H] glutamate uptake was avoided only when three doses of Guo were administered immediately, 24xa0h and 48xa0h after insult, or at 3xa0h, 24xa0h, and 48xa0h after injury or at 6xa0h, 24xa0h, and 48xa0h after HI. These findings indicate that early Guo administration (until 6xa0h) after HI, in three doses may enhance glutamate uptake into brain slices after hypoxia/ischemia, probably resulting in decreased excitotoxicity.

Novel perspectives on swept-source optical coherence tomography

Technologies for multimodal digital imaging of vitreoretinal diseases have improved the accuracy of diagnosis and the depth of the knowledge of the mechanisms of disease and their response to treatments. Optic coherence tomography (OCT) has become a mandatory tool for the management and for the follow-up of retinal pathologies. OCT technology evolved in the last two decades from time-domain to spectral domain and recently to the swept-source OCTs (SS-OCT). SS-OCT improved the depth of imaging and the scan speed, thus adding novel algorithms and features such as for vitreous and vitreoretinal interface evaluation, choroid segmentation and mapping, OCT angiography and En-face OCT. The multimodal approach using SS-OCT is expected to advance the understanding of retinal pathologies such as age related macular degeneration, diabetic maculopathy, central serous chorioretinopathy, the pachychoroid spectrum and macular telangiectasia. Surgical vitreoretinal diseases such as vitreo-macular traction syndrome, epiretinal membrane, retinal detachment, proliferative vitreoretinal retinopathy and diabetic traction retinal detachment also will be better understood and documented with SS-OCT. This technology also provides great utility for a broad spectrum of ophthalmic pathologies including glaucoma, uveitis, tumors and anterior segment evaluation.

Comparative analysis of choroidal thickness in third trimester pregnant women

BackgroundThe impact of pregnancy on the choroid is still under investigation. The aim of this study is to compare choroidal thickness measurements of healthy pregnant women in the third trimester and healthy non-pregnant women using spectral-domain optical coherence tomography (OCT).MethodsThis cross-sectional study included 122 eyes of 61 women, divided into two groups: 27 healthy pregnant women in the third trimester and 34 age-matched healthy non-pregnant women. Choroidal thickness was measured using Enhanced Depth Imaging OCT at ten different locations: at the fovea and every 500xa0µm from the fovea up to 2500xa0µm temporally and up to 2000xa0µm nasally.ResultsThere were no significant differences in the ten measurements of choroidal thickness comparing both groups. Mean subfoveal choroidal thickness was 304.1xa0+xa09.6xa0µm in the control group and 318.1xa0+xa015.6xa0µm in the pregnant women group (pxa0=xa00.446). There was also no statistically significant association between gestational age and choroidal thickness measurements in the healthy pregnant women group.ConclusionsOur study showed no statistically difference in choroidal thickness between healthy non-pregnant women and healthy pregnant women in the third trimester.

Microvascular Complications of Posttransplant Diabetes Mellitus in Kidney Transplant Recipients: a Longitudinal Study Posttransplant Diabetes Complications

ObjectivenTo assesses microvascular complications in renal transplant recipients with posttransplant diabetes mellitus (PTDM).nnnResearch Design and MethodsnIn this observational study, patients with ≥5 years of PTDM were included from a cohort of 895 kidney recipients transplanted from 2000 through 2011. Diabetic retinopathy was evaluated by fundus photographs and optical coherence tomography (OCT). Diabetes kidney disease was evaluated by protein to creatinine ratio (PCR) and estimated glomerular filtration rate (eGFR). Distal polyneuropathy was assessed by Michigan Protocol and 10 g-monofilament feet examinations. The Ewing protocol identified cardiovascular autonomic neuropathy. Renal transplant recipients without PTDM diagnosis (NPTDM) were considered controls.nnnResultsnAfter 144.5 months of follow-up, 135 (15%) patients developed PTDM, and 64 had a PTDM duration ≥5 years. None of the patients with PTDM presented diabetic retinopathy at fundus photographs, but thinning of inner retinal layers was observed with OCT. More than 60% of patients with PTDM had distal polyneuropathy (OR, 1.55; 95% CI, 1.26 to 1.91; P < 0.001). Cardiovascular reflex tests abnormalities were similar between patients with PTDM and NPTDM (P = 0.26). During the first year and 8.5 ± 3.0 years after renal transplantation, eGFR and PCR did not differ significantly between patients with PTDM or NPTDM.nnnConclusionsnThis longitudinal study assesses microvascular complications in renal transplant patients with PTDM. A lower than expected prevalence as well as a different clinical course of the complications was observed. PTDM seems to be a unique type of diabetes, and its consequences may be milder than expected in type 1 and type 2 diabetes.