The nigral control of epilepsy: basal ganglia circuitry as a substrate for seizure control
Hans O Lüders in Deep Brain Stimulation and Epilepsy, 2020
The focally evoked model of seizures first developed in the rat by the unilateral application of bicuculline into the deep layers of the rostral piriform cortex,4 was extended to the monkey in a series of experiments identifying a comparable epileptogenic site in the monkey brain.5–7 The site, which has been referred to as ‘area tempestas’ (AT), is comparable in both rat and monkey to the extent that: (a) relatively low doses of bicuculline when focally applied unilaterally evoke propagated seizures that have the characteristics of complex partial seizures; and (b) as functionally defined by the response to bicuculline, the site is highly circumscribed (<1 mm diameter in the rat and <3 mm diameter in the monkey). By evoking seizures from this site in both rats and monkeys, the two species could be compared for seizure propagation and seizure control mechanisms.
Neurotransmitters and Receptors in the Basal Ganglia
W. R. Wayne Martin in Functional Imaging in Movement Disorders, 2019
GABA is the neurotransmitter used by the majority of neurons in the striatum, lateral and medial pallidum, and the substantia nigra pars reticulata.23,24 Two classes of GABA receptors have been defined, GABAA and GABAB receptors. The GABAA receptors are postsynaptic receptors mediating chloride flux. These receptors are bicuculline-sensitive and are the classic GABA receptors mediating GABAergic inhibition. GABAB receptors also appear to mediate inhibition but through bicuculline-insensitive receptors. The GABAB receptor is located both presynaptically on the terminals of neurons which use transmitters other than GABA and postsynaptically. There are no selective antagonists at the GABAB receptor and the only selective agonist is baclofen.
The Genetically Epilepsy-Prone Rat: Neuronal Networks And Actions Of Amino Acid Neurotransmitters
Carl L. Faingold, Gerhard H. Fromm in Drugs for Control of Epilepsy:, 2019
In the normal rat and the GEPR-9 iontophoretic application of bicuculline onto ICc neurons blocks the inhibitory action of GABA.49 However, higher doses of bicuculline convert the responses of many normal ICc neurons from an onset response to an onset-offset response (Figure 2D), similar to that seen with elevated prevalence in the GEPR-9 (Figure 2B). Many ICc neurons in the GEPR-9 exhibit onset-offset responses only at high stimulus intensities. However, a number of these neurons began to exhibit the onset-offset pattern at lower intensities after bicuculline application.44 The dose of iontophoretically applied bi-cuculline required to induce the onset-offset response is significantly lower in ICc neurons of the GEPR-9 than in the normal rat (Table 4).
3D bioprinting for organ and organoid models and disease modeling
Published in Expert Opinion on Drug Discovery, 2023
Amanda C. Juraski, Sonali Sharma, Sydney Sparanese, Victor A. da Silva, Julie Wong, Zachary Laksman, Ryan Flannigan, Leili Rohani, Stephanie M. Willerth
The intrinsic complexity of the central nervous system (CNS) limits its ability to be replicated using current in vitro 2D models. Accordingly, 3D bioprinting tissue models play an important role in the process of modeling CNS diseases with applications in drug screening. Pharmaceutical research for complex brain diseases, such as Alzheimer’s Disease and Parkinson’s Disease, is often limited by expenses, time, and inadequate pre-clinical models. 3D bioprinting techniques allow for cell-cell interactions that more accurately replicate in vivo tissues, thus offering an improved approach for brain disease modeling and drug screening platform. A study by Gu et al (2018) [13] bioprinted brain organoids with differentiated neurons derived from human neural stem cells (hNSC). The hNSC were well distributed along the organoid and displayed markers for both neuronal and neuroglial markers. They also observed upregulated GABAergic and serotonin neuronal markers, as well as vesicular glutamate and serotonin transporters. Neuronal maturation was observed by both spontaneous and bicuculline (a GABA(A) receptor antagonist) induced calcium response. Mature neurons displayed spontaneous activity, synaptic contacts and established networks. While GABAergic differentiation was predominant, the presence of both glutamatergic and serotonergic activity indicates that the model could be used as a more extensive physiological model that could be used for CNS-oriented drug screening.
Moringa oleifera seed ethanol extract and its active component kaempferol potentiate pentobarbital-induced sleeping behaviours in mice via a GABAergic mechanism
Published in Pharmaceutical Biology, 2022
Wei-Liang Liu, Bai-Fen Wu, Jian-Hua Shang, Xue-Feng Wang, Yun-Li Zhao, Ai-Xiang Huang
Pentobarbital sodium (PENT), flumazenil (FMZ), muscimol (MUS), bicuculline (BIC), sodium carboxymethyl cellulose (CMC-Na), polyoxyethylene sorbitan monooleate (Tween-80, TW) and picrotoxin (PIC) were purchased from Sigma-Aldrich Chemical Inc. (St. Louis, MO, USA). Pentylenetetrazole (PTZ) was obtained from National Institute for Food and Drug Control (Beijing, China), and estazolam tablets (EST) were bought from Huazhong Pharmaceutical Inc. (Wuhan, Hubei, China). Mouse γ-amino butyric acid (GABA) and glutamic (Glu) ELISA kit were purchased from Jiancheng Biotech Inc. (Nanjing, China). KA (≥95%) was purchased from Coolaber Biotech Inc. (Beijing, China). Specific rabbit polyclonal antibodies against GABAA receptors subunits (α1, γ2) or glutamate decarboxylase (GAD65/67) and the corresponding conjugated antirabbit immunoglobulin G-horseradish peroxidase were obtained from Abcam Inc. (Cambridge, UK). Human cerebellar granule cells (HCGC) were purchased from the BeNa Culture Collection Inc. (Beijing, China). Dulbecco’s Modified Eagle’s Medium (DMEM) and foetal bovine serum (FBS) were purchased from GIBCO Inc. (Grand Island, NY, USA). The Cl--sensitive fluorescence probe (SFLUOP) and N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE) were obtained from Invitrogen Inc. (Carlsbad, CA, USA). All other chemical agents used in the study were of analytical grade.
Punicalagin and ellagic acid containing Punica granatum L. fruit rind extract prevents vincristine-induced neuropathic pain in rats: an in silico and in vivo evidence of GABAergic action and cytokine inhibition
Published in Nutritional Neuroscience, 2021
Vivek Jain, Ashutosh Pareek, Yashumati Ratan Bhardwaj, Saurabh Kumar Sinha, Madan Mohan Gupta, Nirmal Singh
In the present investigation, nine groups were employed. Each group contains six rats. Animals were sacrificed on 22nd day and the biochemical estimations were performed as described earlier. The sub-convulsive dose of bicuculline (selective competitive antagonist of GABAA receptors) was chosen from a prior study performed by the Japanese researcher [33] to find out the mechanism of action of PFE. Mechanical hyperalgesia and cold allodynia were performed (after 1st, 2nd, and 3rd h of scheduled treatment) on the16th day. An earlier study of P. granatum fruit extract (100 and 200 mg/kg oral) exhibited antinociceptive effects in diabetic neuropathy [63]. Moreover, another study reported beneficial effects at 100 and 300 mg/kg dose of P. granatum fruit extract in injury-induced neuropathic pain model [18]. The 100 mg/kg, i.p. dose of PFE was chosen according to Patel et al. [34]. That’s why we choose 100 and 300 mg/kg dose in the present study. The protocol of experimental design is shown in Table 1.
Related Knowledge Centers
- Alkaloid
- Cerebral Cortex
- Convulsion
- Corydalis
- Gabaa Receptor
- Glutamatergic
- Receptor Antagonist
- Hippocampus
- Epilepsy
- Phthalide
- Gabaa Receptor