Anterior thalamic nuclei deep brain stimulation reduces disruption of the blood–brain barrier, albumin extravasation, inflammation and apoptosis in kainic acid-induced epileptic rats

Chen, Ying; Zhu, Guanyu; Wang, Xiu; Shi, Lin; Du, Tingting; Liu, Defeng; Liu, Yu-Ye; Jiang, Yin; Zhang, Xin; Zhang, Jianguo

doi:10.1080/01616412.2017.1379241

Cited by 20 publications

(17 citation statements)

References 31 publications

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“…Altered BBB permeability has been documented in experimental epilepsy models and human surgically resected epileptic tissue [ 31 , 32 , 33 ]. BBB alteration is also induced by the IPE and thus it is thought to be involved in the epileptogenic process [ 31 , 34 ]. We here studied the astroglial aquaporin-4 (AQP4), a protein highly expressed in the astroglial end-feet forming an essential part of the BBB.…”

Section: Resultsmentioning

confidence: 99%

Early Gabapentin Treatment during the Latency Period Increases Convulsive Threshold, Reduces Microglial Activation and Macrophage Infiltration in the Lithium-Pilocarpine Model of Epilepsy

et al. 2017

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The lithium-pilocarpine model of epilepsy reproduces several features of temporal lobe epilepsy in humans, including the chronological timeline of an initial latency period followed by the development of spontaneous seizures. Epilepsy therapies in humans are implemented, as a rule, after the onset of the spontaneous seizures. We here studied the potential effect on epileptogenesis of starting an early treatment during the latency period, in order to prevent the development of spontaneous seizures. Adult male Wistar rats were treated with 3 mEq/kg LiCl, and 20 h later 30 mg/kg pilocarpine. Once status epilepticus (SE) was achieved, it was allowed to last for 20 min, and then motor seizures were controlled with the administration of 20 mg/kg diazepam. At 1DPSE (DPSE, days post-status epilepticus), animals started to receive 400 mg/kg/day gabapentin or saline for 4 days. At 5DPSE, we observed that SE induced an early profuse microglial and astroglial reactivity, increased synaptogenic trombospondin-1 expression and reduced AQP4 expression in astroglial ending feet. Blood brain barrier (BBB) integrity seemed to be compromised, as infiltrating NG2+ macrophages and facilitated access to the CNS was observed by transplanting eGFP+ blood cells and bone marrow-derived progenitors in the SE animals. The early 4-day gabapentin treatment successfully reduced microglial cell reactivity and blood-borne cell infiltration, without significantly altering the mRNA of proinflammatory cytokines IL-1β and TNFα immediately after the treatment. After 21DSPE, another group of animals that developed SE and received 4 days of gabapentin treatment, were re-exposed to subconvulsive accumulative doses of pilocarpine (10 mg/kg/30 min) and were followed by recording the Racine scale reached. Early 4-day gabapentin treatment reduced the Racine scale reached by the animals, reduced animal mortality, and reduced the number of animals that achieved SE (34% vs. 72%). We conclude that early gabapentin treatment following SE, during the latency period, is able to reduce neuroinflammation and produces a persistent effect that limits seizures and increases convulsive threshold, probably by restricting microglial reactivity and spurious synaptogenesis.

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Section: Resultsmentioning

confidence: 99%

Early Gabapentin Treatment during the Latency Period Increases Convulsive Threshold, Reduces Microglial Activation and Macrophage Infiltration in the Lithium-Pilocarpine Model of Epilepsy

et al. 2017

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“…[ [45][46][47][48][49][50] Serum albumin injection Intracerebroventricular injection of 1.9 mM in rats.…”

Section: Dose/methods Outcome Referencesmentioning

confidence: 99%

“…There is also a higher number of GFAP-positive cells which shows that kainic acid promotes gliosis, also an indicator of neuroinflammation. Chen, Zhu [49] found that kainic acid administration causes swelling and deformities of endothelial cells and their nuclei in cerebromicrovessels. The BBB integrity is also destroyed following kainic acid injection with signs of vacuolation, perivascular edema and membrane damage [49].…”

Section: Kainic Acid (Ka) Injectionmentioning

confidence: 99%

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Inflammation: Cause or Consequence of Epilepsy?

Lee¹,

Shaikh²

2019

Epilepsy - Advances in Diagnosis and Therapy

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Epilepsy is the third most common neurological disorder, affecting about 70 million people worldwide. It is defined as a central nervous system disorder which affects the neuronal activity in the brain, causing unprovoked seizures and other behavioral changes. Unfortunately, one-third of epilepsy patients are unresponsive to available therapies and patients who respond to antiepileptic drugs often complain of debilitating side effects. In the effort of devising a suitable therapy for epilepsy treatment, researchers delved into the origin of seizures and the epileptogenic process and found an association between epilepsy and inflammation. Here, we discuss the involvement of inflammatory mediators in the development and progression of seizures and epileptogenesis, supported by clinical shreds of evidence. Subsequently, we discuss the role of inflammation in the generation of seizures, as it is debatable whether inflammation is the cause or consequence of epilepsy, along with experimental models in inflammation and epilepsy research.

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“…Notably, electrical stimulation can elicit other cellular responses, such as cell proliferation. 19 Interestingly, electrical stimulation has been shown to increase the number of blood vessels in the injured brain, 42 modulate blood-brain barrier permeability, 43,44 and modulate numbers of microglia and astrocytes. [45][46][47][48] The ability to affect the microenvironment creates the possibility of ''side effects'' such as modulation of the number of astrocytes and microglia but with more insight into the effects of EFs on tissue responses; these ''side effects'' could be purposely controlled to create an environment more amenable to tissue repair.…”

Section: Nurture: Extrinsic Microenvironment Factors Influencing Migrmentioning

confidence: 99%

Novel Electrode Designs for Neurostimulation in Regenerative Medicine: Activation of Stem Cells

et al. 2020

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Neural stem and progenitor cells (i.e., neural precursors) are found within specific regions in the central nervous system and have great regenerative capacity. These cells are electrosensitive and their behavior can be regulated by the presence of electric fields (EFs). Electrical stimulation is currently used to treat neurological disorders in a clinical setting. Herein we propose that electrical stimulation can be used to enhance neural repair by regulating neural precursor cell (NPC) kinetics and promoting their migration to sites of injury or disease. We discuss how intrinsic and extrinsic factors can affect NPC migration in the presence of an EF and how this impacts electrode design with the goal of enhancing tissue regeneration. We conclude with an outlook on future clinical applications of electrical stimulation and highlight technological advances that would greatly support these applications.

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Anterior thalamic nuclei deep brain stimulation reduces disruption of the blood–brain barrier, albumin extravasation, inflammation and apoptosis in kainic acid-induced epileptic rats

Cited by 20 publications

References 31 publications

Early Gabapentin Treatment during the Latency Period Increases Convulsive Threshold, Reduces Microglial Activation and Macrophage Infiltration in the Lithium-Pilocarpine Model of Epilepsy

Early Gabapentin Treatment during the Latency Period Increases Convulsive Threshold, Reduces Microglial Activation and Macrophage Infiltration in the Lithium-Pilocarpine Model of Epilepsy

Inflammation: Cause or Consequence of Epilepsy?

Novel Electrode Designs for Neurostimulation in Regenerative Medicine: Activation of Stem Cells

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