Probing Caffeine Administration as a Medical Management for Hydrocephalus: An Experimental Study

Olopade, Funmilayo; Femi-Akinlosotu, Omowumi; Ibitoye, Chloe; Shokunbi, Temitayo

doi:10.1016/j.pediatrneurol.2022.07.003

Cited by 4 publications

(5 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There is no ideal animal model for hydrocephalus, due to the multifactorial nature of its pathophysiology and the fact that no model can fully mimic the human condition yet (37)(38)(39)(40). The most recognized method of effectively inducing hydrocephalus in animals especially rodents is by intracisternal injection of sterile kaolin (aluminum silicate) which was used in this study, which has been known to cause an inflammatory reaction and meningeal scarring leading to an obstructive hydrocephalic condition (23,38,41). This model has contributed significantly to the understanding of the pathogenesis of hydrocephalus (41).…”

Section: Discussionmentioning

confidence: 99%

“…This model has contributed significantly to the understanding of the pathogenesis of hydrocephalus ( 41 ). The brain of juvenile mice (three-week old) is developmentally similar to that of a human infant ( 23 , 42 ), Thus, cisternal kaolin injection in juvenile rodents is a reasonable model for studying infantile hydrocephalus ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

“…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%

“…Damage to the hippocampus due to hydrocephalus may cause loss in its cognitive, learning and memory functions ( 20 , 22 ). Hydrocephalus has been known to cause inflammation, myelin disruption, axonal damage within the periventricular white matter and loss in oligodendrocytes ( 20 , 23 – 25 ). The current standard definitive treatment for established hydrocephalus is surgical diversion of CSF, but this is expensive and associated complications such as shunt obstruction and infections.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

show abstract

“…Administration of caffeine to dams reduced cell death, and increased the neurons dendritic arborization in the sensorimotor cortex and striatum of the mice neonates and improved hydrocephalic deficits and behavioral development [119] Anti-inflammatory effect…”

Section: Hydrocephalusmentioning

confidence: 99%

Overview of Caffeine Effects on Human Health and Emerging Delivery Strategies

Saraiva¹,

Jacinto²,

Gonçalves³

et al. 2023

Preprint

View full text Add to dashboard Cite

Caffeine is a naturally occurring alkaloid found in various plants. It acts as a stimulant, antioxidant, anti-inflammatory and even an aid in pain management, and is found in several over-the-counter medications. This naturally derived bioactive compound is the best-known ingredient in coffee and other beverages, such as tea, soft drinks, and energy drinks, and is the most widely consumed substance worldwide. Therefore, it is extremely important to research the effects of this substance on the human body. With this in mind, caffeine and its derivatives have been extensively studied to evaluate its ability to prevent diseases and exert anti-aging and neuroprotective effects. This review is intended to provide an overview of the effects of caffeine on cancer, cardiovascular, immunological, inflammatory, and neurological diseases, among others. The heavily researched area of caffeine in sports will also be discussed. Finally, recent advances in the development of novel formulations, in the form of dietary supplements of caffeine and nanocarriers, to enhance the bioavailability of caffeine and its beneficial effects will be discussed. On the other hand, caffeine may contribute to elevated blood pressure, anemia, and migraine.

show abstract

Normal Pressure Hydrocephalus in Adult Mice Causes Gait Impairment, Cognitive Deficits, and Urinary Frequency with Incontinence

Tish,

Voss,

Bertolli

et al. 2024

eNeuro

View full text Add to dashboard Cite

Normal pressure hydrocephalus (NPH) is marked by enlarged cerebral ventricles with normal intracranial pressure, plus three stereotypical symptoms: gait impairment, cognitive dysfunction, and urinary frequency with urge-incontinence. The neural circuit dysfunction responsible for each of these symptoms remains unknown, and an adult mouse model would expand opportunities to explore these mechanisms in preclinical experiments. Here, we describe the first mouse model of chronic, communicating hydrocephalus with normal intracranial pressure. Hydrocephalic male and female mice had unsteady gait and reduced maximum velocity. Despite performing well on a variety of behavioral tests, they exhibited subtle learning impairments. Hydrocephalic mice also developed urinary frequency, and many became incontinent. This mouse model, with symptoms resembling human NPH, can be combined with molecular-genetic tools in any mouse strain to explore the neural circuit mechanisms of these symptoms. Preclinical work using this hydrocephalus model will lead to the development of new treatments for NPH symptoms.Significance StatementLike human patients with normal pressure hydrocephalus (NPH), mice with communicating hydrocephalus develop enlarged cerebral ventricles with normal intracranial pressure plus three stereotypical symptoms: gait impairment, cognitive dysfunction, and urinary frequency with incontinence. This mouse model, with symptoms resembling human NPH, can be combined with molecular-genetic tools in any mouse strain to explore neural circuit mechanisms of NPH symptoms.

show abstract

Probing Caffeine Administration as a Medical Management for Hydrocephalus: An Experimental Study

Cited by 4 publications

References 56 publications

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

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

Overview of Caffeine Effects on Human Health and Emerging Delivery Strategies

Normal Pressure Hydrocephalus in Adult Mice Causes Gait Impairment, Cognitive Deficits, and Urinary Frequency with Incontinence

Contact Info

Product

Resources

About