The therapeutic potential and efficiency of Intracerebroventricular transplantation and intravenous injection of Mesenchymal stem cells in relieving Aß hallmarks and improving cognitive dysfunction in AD induced model

Anwar, Mai M.; Ali, Ola; Rashed, Laila Ahmed; Badawi, Ayman M.; Eltablawy, Nadia A.

doi:10.1016/j.genrep.2021.101323

Cited by 7 publications

(11 citation statements)

References 49 publications

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“…Our previous results indicated the efficiency of exogenous hydrogen sulphide donor and MSCs (whether systemic or localized administration) in hindering AD progression and even may act as a successful prophylactic protocol due to their anti-inflammatory, antioxidant, immunomodulating response, and Aβ engulfing actions due to the activation of Microglia M2 anti-inflammatory type over M1 microglia proinflammatory type (Anwar et al 2018(Anwar et al , 2019b(Anwar et al , 2021bAnwar 2019). Our results revealed that the administration of NaHS as an exogenous hydrogen sulphide donor and MSCs alleviated neuroinflammatory AD damageable drawbacks on the liver and heart by decreasing Aβ, cholesterol, triglycerides, and, inflammatory cytokines in serum levels.…”

Section: Discussionmentioning

confidence: 99%

“…Alzheimer’s disease (AD) is one of the most common types of aging-related neurological disorders that manifests in the form of personal behavior changes, irritability, memory loss, and cognitive dysfunctions (Heneka et al 2015 ; Uddin et al 2022 ). The pathological drawbacks of AD are related to severe neuronal death that results in a major reduction of the brain’s volume, synaptic transmissions, and metabolic capacity (Toral-Rios et al 2020 ; Anwar 2021 , 2021a ; Xia et al 2020 ). Neuroinflammatory AD-associated neuronal death is mainly manifested due to tau and Aβ depositions resulting in an abnormal metabolic system and exaggerated apoptosis.…”

Section: Introductionmentioning

confidence: 99%

“…Mesenchymal stem cells (MSCs), are adult stem cells type capable of continuous self-renewal and tissue differentiation. They are mainly found in the bone marrow (BM) and can also be identified in several tissues including muscles, adipose tissue, peripheral blood, and the umbilical cord (Hmadcha et al 2020 ; Anwar et al 2021a ). When MSCs are cultured under controlled conditions, they can be capable of differentiating into different cells such as cardiomyocytes, neuronal cells hepatocytes, and epithelial cells.…”

Section: Introductionmentioning

confidence: 99%

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Hepatic and cardiac implications of increased toxic amyloid-beta serum level in lipopolysaccharide-induced neuroinflammation in rats: new insights into alleviating therapeutic interventions

Anwar

Mabrouk

2023

Inflammopharmacol

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Neuroinflammation is a devastating predisposing factor for Alzheimer’s disease (AD). A number of clinical findings have reported peripheral disorders among AD patients. Amyloid beta (Aβ) is a toxic physiological aggregate that serves as a triggering factor for hepatic and cardiac disorders related to neurotoxicity. As a drawback of Aβ excessive accumulation in the brain, part of Aβ is believed to readily cross the blood–brain barrier (BBB) into the peripheral circulation resulting in serious inflammatory and toxic cascades acting as a direct bridge to cardiac and hepatic pathophysiology. The main aim is to find out whether neuroinflammation-related AD may result in cardiac and liver dysfunctions. Potential therapeutic interventions are also suggested to alleviate AD’s cardiac and hepatic defects. Male rats were divided into: control group I, lipopolysaccharide (LPS)-neuroinflammatory-induced group II, LPS-neuroinflammatory-induced group treated with sodium hydrogen sulphide donor (NaHS) (group III), and LPS-neuroinflammatory-induced group treated with mesenchymal stem cells (MSCs) (group IV). Behavior and histopathological studies were conducted in addition to the estimation of different biological biomarkers. It was revealed that the increased toxic Aβ level in blood resulted in cardiac and hepatic malfunctions as a drawback of exaggerated inflammatory cascades. The administration of NaHS and MSCs proved their efficiency in combating neuroinflammatory drawbacks by hindering cardiac and hepatic dysfunctions. The consistent direct association of decreased heart and liver functions with increased Aβ levels highlights the direct involvement of AD in other organ complications. Thereby, these findings will open new avenues for combating neuroinflammatory-related AD and long-term asymptomatic toxicity. Graphic abstract

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hepatic and cardiac implications of increased toxic amyloid-beta serum level in lipopolysaccharide-induced neuroinflammation in rats: new insights into alleviating therapeutic interventions

Anwar

Mabrouk

2023

Inflammopharmacol

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“…Rats were trained for three consecutive days, each lasting 60 s per rat. On day 7, a final test was conducted where the time taken by each rat to reach the platform was directly recorded and calculated ( Anwar et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Assessing the role of primary healthy microglia and gap junction blocker in hindering Alzheimer’s disease neuroinflammatory type: Early approaches for therapeutic intervention

et al. 2023

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Alzheimer’s disease (AD) is a predominantly heterogeneous disease with a highly complex pathobiology. The presence of amyloid-beta (Aβ) depositions and the accumulation of hyperphosphorylated tau protein remain the characteristic hallmarks of AD. These hallmarks can be detected throughout the brain and other regions, including cerebrospinal fluid (CSF) and the spinal cord. Microglia cells, the brain-resident macrophage type of the brain, are implicated in maintaining healthy brain homeostasis. The localized administration of primary healthy microglia (PHM) is suggested to play a role in mitigating AD hallmark depositions and associated cognitive dysfunction. Carbenoxolone (CBX) is the most common gap junction blocker. It cannot effectively cross the blood–brain barrier (BBB) under systemic administration. Therefore, localized administration of CBX may be a recommended intervention against AD by acting as an antioxidant and anti-inflammatory agent. This study aims to determine whether the localized intracerebroventricular (ICV) administration of PHM and CBX may act as an effective therapeutic intervention for AD neuroinflammatory type. In addition, this study also aims to reveal whether detecting AD hallmarks in the spinal cord and CSF can be considered functional and effective during AD early diagnosis. Male albino rats were divided into four groups: control (group 1), lipopolysaccharide (LPS)-induced AD neuroinflammatory type (group 2), ICV injection of LPS + isolated PHM (group 3), and ICV injection of LPS + CBX (group 4). Morris water maze (MWM) was conducted to evaluate spatial working memory. The brain and spinal cord were isolated from each rat with the collection of CSF. Our findings demonstrate that the localized administration of PHM and CBX can act as promising therapeutic approaches against AD. Additionally, Aβ and tau toxic aggregates were detected in the spinal cord and the CSF of the induced AD model concomitant with the brain tissues. Overall, it is suggested that the ICV administration of PHM and CBX can restore normal brain functions and alleviate AD hallmark depositions. Detecting these depositions in the spinal cord and CSF may be considered in AD early diagnosis. As such, conducting clinical research is recommended to reveal the benefits of related therapeutic approaches compared with preclinical findings.

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“…HSV‐1 infection whether reached the CNS directly or indirectly was found to affect different brain regions resulting in severe neuroinflammation and leading eventually to progressive AD pathology. Once reaching the CNS, the virus directly begins to replicate along with the release of pathogen‐associated molecular patterns (PAMPs) and damage‐associated molecular patterns (DAMPs) leading to lipopolysaccharides (LPS) like effects 35–40 . Consequently, this results in the activation and release of pro‐inflammatory cytokines, chemokines, and reactive oxygen species (ROS) associated with TNF‐α and NF‐kB.…”

Section: Herpes Simplex Virus Type 1 (Hsv‐1) and Alzheimer's Diseasementioning

confidence: 99%

The emerging mechanism behind viral infections and extracellular vesicles hypotheses leading to neuroinflammation and Alzheimer's disease pathology

Anwar

2023

Ibrain

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Despite decades of repeated and intense research, the etiology of sudden Alzheimer's disease (AD) symptoms is still unclear. AD progressive pathology mainly involves neuron damage, depositions of amyloid‐beta (Aβ), and hyperphosphorylated tau protein. All these defects are manifested by exaggerated cytokine storm and neuroinflammation leading to irreversible brain damage in the long term. Despite the numerous risks and drawbacks associated with AD, it is believed that there is a hidden unknown causative and predisposing factors for AD. Extracellular vesicles (EVs) are small vesicles released by cells as a type of intercellular communication. Several pieces of evidence support the inclusion of viral components within EVs facilitating their penetration into the blood–brain barrier leading to neuroinflammation. In light of the SARS‐CoV‐19 pandemic and its related neurological complications, it is mandatory to highlight the possibility and viability of viral infections such as varicella‐zoster virus (VZV) and herpes simplex virus (HSV) on the onset of AD. Herein, the author is investigating the potential role of VZV and HSV along with highlighting the suggested route of pathogenesis entry resulting in AD manifestations. Additionally, this review aims to summarize the role of EVs in mediating the central nervous system viral infections leading to AD.

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The therapeutic potential and efficiency of Intracerebroventricular transplantation and intravenous injection of Mesenchymal stem cells in relieving Aß hallmarks and improving cognitive dysfunction in AD induced model

Cited by 7 publications

References 49 publications

Hepatic and cardiac implications of increased toxic amyloid-beta serum level in lipopolysaccharide-induced neuroinflammation in rats: new insights into alleviating therapeutic interventions

Hepatic and cardiac implications of increased toxic amyloid-beta serum level in lipopolysaccharide-induced neuroinflammation in rats: new insights into alleviating therapeutic interventions

Assessing the role of primary healthy microglia and gap junction blocker in hindering Alzheimer’s disease neuroinflammatory type: Early approaches for therapeutic intervention

The emerging mechanism behind viral infections and extracellular vesicles hypotheses leading to neuroinflammation and Alzheimer's disease pathology

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