Melatonin Attenuates Histopathological Changes in the Hippocampus of Infantile Rats with Kaolin-Induced Hydrocephalus

Turğut, Mehmet; Baka, Meral; Uyanıkgil, Yiğit

doi:10.1159/000488497

Cited by 7 publications

(4 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Hydrocephalus is a serious problem in sub-Saharan Africa (Salvador et al, 2014). It is an incapacitating disorder (Turgut et al, 2018) affecting 0.2–3.5/1,000 healthy births (Krause et al, 2018) and is the most common neurologic disorder requiring surgery in children (Vogel et al, 2012). The structural changes in the brain that accompany this disorder have been well described.…”

Section: Introductionmentioning

confidence: 99%

Dendritic and Synaptic Degeneration in Pyramidal Neurons of the Sensorimotor Cortex in Neonatal Mice With Kaolin-Induced Hydrocephalus

2019

View full text Add to dashboard Cite

Obstructive hydrocephalus is a brain disorder in which the circulation of cerebrospinal fluid (CSF) is altered in a manner that causes expansion of fluid-filled intracranial compartments particularly the ventricles. The pyramidal neurons of the sensorimotor cortex are excitatory in nature and their dendritic spines are targets of excitatory synapses. This study evaluated the effect of hydrocephalus on dendritic arborization and synaptic structure of the pyramidal neurons of the sensorimotor cortex of neonatal hydrocephalic mice. Sterile kaolin suspension (0.01 ml of 250 mg/mL) was injected intracisternally into day old mice. Control animals mice received sham injections. Pups were weighed and sacrificed on postnatal days (PND) 7, 14 and 21. Fixed brain tissue blocks were silver impregnated using a modified Golgi staining technique and immunolabeled with synaptophysin to determine dendritic morphology and synaptic integrity respectively. Data were analyzed using ANOVA at α 0.05 . Golgi staining revealed diminished arborization of the basal dendrites and loss of dendritic spines in the pyramidal neurons of hydrocephalic mice. Compared to age-matched controls, there was a significant reduction in the percentage immunoreactivity of anti-synaptophysin in hydrocephalic mice on PND 7 (14.26 ± 1.91% vs. 62.57 ± 9.40%), PND 14 (4.19 ± 1.57% vs. 93.01 ± 1.66%) and PND 21 (17.55 ± 2.76% vs. 99.11 ± 0.63%) respectively. These alterations suggest impaired neuronal connections that are essential for the development of cortical circuits and may be the structural basis of the neurobehavioral deficits observed in neonatal hydrocephalus.

show abstract

Section: Introductionmentioning

confidence: 99%

Dendritic and Synaptic Degeneration in Pyramidal Neurons of the Sensorimotor Cortex in Neonatal Mice With Kaolin-Induced Hydrocephalus

2019

View full text Add to dashboard Cite

show abstract

“…In the quest for finding non-surgical means of treating hydrocephalus, several experimental methods have been explored including use of intraperitoneal injection of deferoxamine, a chelating agent that binds free ferric iron (Fe 3+ ) which was found to have neuroprotective and anti-fibrotic properties in experimental animals with hydrocephalus ( 43 – 45 ). Anti-inflammatory, anti-oxidative, neuronal and axonal protection interventions by use of intraperionteal injection of Minocycline ( 46 – 48 ), epigalloctechin gallate from green tea and N-acetylcystein ( 27 , 49 ), melatonin ( 50 , 51 ), memantine ( 52 ) and caffeine ( 23 ) have been reported to offer neuroprotection in experimental hydrocephalic conditions. Vanadium compound which has been reported to possess antioxidant properties and which promotes neuroprotection and cell recovery in neurotrauma and neurodegenerative disorders ( 12 , 17 , 53 , 54 ) has not been previously studied for possible beneficial effect in hydrocephalus.…”

Section: Discussionmentioning

confidence: 99%

Vanadium improves memory and spatial learning and protects the pyramidal cells of the hippocampus in juvenile hydrocephalic mice

Femi-Akinlosotu

Olopade²,

Obiako³

et al. 2023

Front. Neurol.

View full text Add to dashboard Cite

BackgroundHydrocephalus is a neurological condition known to cause learning and memory disabilities due to its damaging effect on the hippocampal neurons, especially pyramidal neurons. Vanadium at low doses has been observed to improve learning and memory abilities in neurological disorders but it is uncertain whether such protection will be provided in hydrocephalus. We investigated the morphology of hippocampal pyramidal neurons and neurobehavior in vanadium-treated and control juvenile hydrocephalic mice.MethodsHydrocephalus was induced by intra-cisternal injection of sterile-kaolin into juvenile mice which were then allocated into 4 groups of 10 pups each, with one group serving as an untreated hydrocephalic control while others were treated with 0.15, 0.3 and 3 mg/kg i.p of vanadium compound respectively, starting 7 days post-induction for 28 days. Non-hydrocephalic sham controls (n = 10) were sham operated without any treatment. Mice were weighed before dosing and sacrifice. Y-maze, Morris Water Maze and Novel Object Recognition tests were carried out before the sacrifice, the brains harvested, and processed for Cresyl Violet and immunohistochemistry for neurons (NeuN) and astrocytes (GFAP). The pyramidal neurons of the CA1 and CA3 regions of the hippocampus were assessed qualitatively and quantitatively. Data were analyzed using GraphPad prism 8.ResultsEscape latencies of vanadium-treated groups were significantly shorter (45.30 ± 26.30 s, 46.50 ± 26.35 s, 42.99 ± 18.44 s) than untreated group (62.06 ± 24.02 s) suggesting improvements in learning abilities. Time spent in the correct quadrant was significantly shorter in the untreated group (21.19 ± 4.15 s) compared to control (34.15 ± 9.44 s) and 3 mg/kg vanadium-treated group (34.35 ± 9.74 s). Recognition index and mean % alternation were lowest in untreated group (p = 0.0431, p=0.0158) suggesting memory impairments, with insignificant improvements in vanadium-treated groups. NeuN immuno-stained CA1 revealed loss of apical dendrites of the pyramidal cells in untreated hydrocephalus group relative to control and a gradual reversal attempt in the vanadium-treated groups. Astrocytic activation (GFAP stain) in the untreated hydrocephalus group were attenuated in the vanadium-treated groups under the GFAP stain. Pyknotic index in CA1 pyramidal layer of untreated (18.82 ± 2.59) and 0.15mg/kg vanadium-treated groups (18.14 ± 5.92) were significantly higher than control (11.11 ± 0.93; p = 0.0205, p = 0.0373) while there was no significant difference in CA3 pyknotic index across all groups.ConclusionOur results suggest that vanadium has a dose-dependent protective effect on the pyramidal cells of the hippocampus and on memory and spatial learning functions in juvenile hydrocephalic mice.

show abstract

“…that there was no increase in neuronal density of hydrocephalic rats compared to the control rats in both acute and chronic stages of hydrocephalus. and McAllister, 2000;Del Bigio, 2003;Cabuk et al, 2011;Taveira et al, 2012;Karinna et al, 2013;Turgut et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Structural and functional deficits of the hippocampus in hydrocephalic rats: the role of age at onset and duration of disease

Shokunbi¹,

Femi-Akinlosotu²,

Olopade³

et al. 2023

EJA

View full text Add to dashboard Cite

We studied the pyramidal neurons of the hippocampus in neonatal, juvenile and adult rats with hydrocephalus of varying durations and related these changes to their learning and memory. Hydrocephalus was induced in 7-day-old neonates, 4-week-old juvenile and 16-week-old adult Albino rats by intra-cisternal injection 0.02-0.04 ml of 150mg/ml of kaolin in sterile water (150 mg/ml). We studied escape latency and platform crossings with the Morris water maze prior to animal sacrifice at 2 and 4 weeks post induction in neonates and at 4 and 8 weeks post induction in juveniles and adults. We examined pyramidal neurons with cresyl violet and modified Golgi stain and analyzed behavioural scores and pyknotic indices. Statistical significance was determined at p<0.05. The basal dendrites of the pyramidal neurons were reduced in the hydrocephalic groups. In the CA1, the pyknotic index was significantly increased in both groups of hydrocephalic neonates but only in hydrocephalic juveniles and adults sacrificed at 4 weeks. In the CA3 it was increased in hydrocephalic neonates sacrificed at 2 weeks and hydrocephalic juveniles sacrificed at 4 weeks. The escape latency was greater and the number of platform crossing was lower in the hydrocephalic rats than in their age matched controls. Pyramidal neurons were morphologically altered in hydrocephalus, in association with changes in spatial learning and memory. The CA1 region in young animals was particularly vulnerable. Functional recovery occurs with time and to a greater extent in older animals.

show abstract

Melatonin Attenuates Histopathological Changes in the Hippocampus of Infantile Rats with Kaolin-Induced Hydrocephalus

Cited by 7 publications

References 40 publications

Dendritic and Synaptic Degeneration in Pyramidal Neurons of the Sensorimotor Cortex in Neonatal Mice With Kaolin-Induced Hydrocephalus

Dendritic and Synaptic Degeneration in Pyramidal Neurons of the Sensorimotor Cortex in Neonatal Mice With Kaolin-Induced Hydrocephalus

Vanadium improves memory and spatial learning and protects the pyramidal cells of the hippocampus in juvenile hydrocephalic mice

Structural and functional deficits of the hippocampus in hydrocephalic rats: the role of age at onset and duration of disease

Contact Info

Product

Resources

About