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Article ; Online: Periodic and aperiodic changes to cortical EEG in response to pharmacological manipulation.

Salvatore, Sofia V / Lambert, Peter M / Benz, Ann / Rensing, Nicholas R / Wong, Michael / Zorumski, Charles F / Mennerick, Steven

Journal of neurophysiology

2024 Volume 131, Issue 3, Page(s) 529–540

Abstract: Cortical electroencephalograms (EEGs) may help understanding of neuropsychiatric illness and new treatment mechanisms. The aperiodic component (1/ ...

Abstract	Cortical electroencephalograms (EEGs) may help understanding of neuropsychiatric illness and new treatment mechanisms. The aperiodic component (1/
MeSH term(s)	Male ; Female ; Mice ; Animals ; Electroencephalography ; Receptors, GABA-A ; Ketamine/pharmacology ; gamma-Aminobutyric Acid
Chemical Substances	Receptors, GABA-A ; Ketamine (690G0D6V8H) ; gamma-Aminobutyric Acid (56-12-2)
Language	English
Publishing date	2024-02-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	80161-6
ISSN	1522-1598 ; 0022-3077
ISSN (online)	1522-1598
ISSN	0022-3077
DOI	10.1152/jn.00445.2023
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Article: Spatial and Amplitude Dynamics of Neurostimulation: Insights from the Acute Intrahippocampal Kainate Seizure Mouse Model.

Foutz, Thomas J / Rensing, Nicholas / Han, Lirong / Durand, Dominique M / Wong, Michael

bioRxiv : the preprint server for biology

2023

Abstract: Objective: Neurostimulation is an emerging treatment for patients with medically refractory epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients ...

Abstract	Objective: Neurostimulation is an emerging treatment for patients with medically refractory epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients continue to have persistent seizures even after years of empirical optimization. The objective of this study is to determine optimal spatial and amplitude properties of neurostimulation in inhibiting epileptiform activity in an acute hippocampal seizure model. Methods: We performed high-throughput testing of high-frequency focal brain stimulation in the acute intrahippocampal kainic acid mouse model of temporal lobe epilepsy. We evaluated combinations of six anatomic targets and three stimulus amplitudes. Results: We found that the spike-suppressive effects of high-frequency neurostimulation are highly dependent on the stimulation amplitude and location, with higher amplitude stimulation being significantly more effective. Epileptiform spiking activity was significantly reduced with ipsilateral 250 μA stimulation of the CA1 and CA3 hippocampal regions with 21.5% and 22.2% reductions, respectively. In contrast, we found that spiking frequency and amplitude significantly increased with stimulation of the ventral hippocampal commissure. We further found spatial differences with broader effects from CA1 versus CA3 stimulation. Significance: These findings demonstrate that the effects of therapeutic neurostimulation in an acute hippocampal seizure model are highly dependent on the location of stimulation and stimulus amplitude. We provide a platform to optimize the anti-seizure effects of neurostimulation, and demonstrate that an exploration of the large electrical parameter and location space can improve current modalities for treating epilepsy. Key points: Evaluated spatial and temporal parameters of neurostimulation in a mouse model of acute seizuresBrief bursts of high-frequency (100 Hz) stimulation effectively interrupted epileptiform activity.The suppressive effect was highly dependent on stimulation amplitude and was maximal at the ipsilateral CA1 and CA3 regions.Pro-excitatory effects were identified with high-amplitude high-frequency stimulation at the ventral hippocampal commissure and contralateral CA1.
Language	English
Publishing date	2023-03-09
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.03.07.531440
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Article ; Online: Spatial and amplitude dynamics of neurostimulation: Insights from the acute intrahippocampal kainate seizure mouse model.

Foutz, Thomas J / Rensing, Nicholas / Han, Lirong / Durand, Dominique M / Wong, Michael

Epilepsia open

2023 Volume 9, Issue 1, Page(s) 210–222

Abstract: Objective: Neurostimulation is an emerging treatment for patients with drug-resistant epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients ... ...

Abstract	Objective: Neurostimulation is an emerging treatment for patients with drug-resistant epilepsy, which is used to suppress, prevent, and terminate seizure activity. Unfortunately, after implantation and despite best clinical practice, most patients continue to have persistent seizures even after years of empirical optimization. The objective of this study is to determine optimal spatial and amplitude properties of neurostimulation in inhibiting epileptiform activity in an acute hippocampal seizure model. Methods: We performed high-throughput testing of high-frequency focal brain stimulation in the acute intrahippocampal kainic acid mouse model of status epilepticus. We evaluated combinations of six anatomic targets and three stimulus amplitudes. Results: We found that the spike-suppressive effects of high-frequency neurostimulation are highly dependent on the stimulation amplitude and location, with higher amplitude stimulation being significantly more effective. Epileptiform spiking activity was significantly reduced with ipsilateral 250 μA stimulation of the CA1 and CA3 hippocampal regions with 21.5% and 22.2% reductions, respectively. In contrast, we found that spiking frequency and amplitude significantly increased with stimulation of the ventral hippocampal commissure. We further found spatial differences with broader effects from CA1 versus CA3 stimulation. Significance: These findings demonstrate that the effects of therapeutic neurostimulation in an acute hippocampal seizure model are highly dependent on the location of stimulation and stimulus amplitude. We provide a platform to optimize the anti-seizure effects of neurostimulation, and demonstrate that an exploration of the large electrical parameter and location space can improve current modalities for treating epilepsy. Plain language summary: In this study, we tested how electrical pulses in the brain can help control seizures in mice. We found that the electrode's placement and the stimulation amplitude had a large effect on outcomes. Some brain regions, notably nearby CA1 and CA3, responded positively with reduced seizure-like activities, while others showed increased activity. These findings emphasize that choosing the right spot for the electrode and adjusting the strength of electrical pulses are both crucial when considering neurostimulation treatments for epilepsy.
MeSH term(s)	Humans ; Mice ; Animals ; Kainic Acid ; Epilepsy/therapy ; Hippocampus ; Brain ; Disease Models, Animal ; Status Epilepticus/chemically induced ; Status Epilepticus/therapy
Chemical Substances	Kainic Acid (SIV03811UC)
Language	English
Publishing date	2023-11-30
Publishing country	United States
Document type	Journal Article
ISSN	2470-9239
ISSN (online)	2470-9239
DOI	10.1002/epi4.12861
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Article ; Online: Cerebral vascular and blood brain-barrier abnormalities in a mouse model of epilepsy and tuberous sclerosis complex.

Guo, Dongjun / Zhang, Bo / Han, Lirong / Rensing, Nicholas R / Wong, Michael

Epilepsia

2023 Volume 65, Issue 2, Page(s) 483–496

Abstract: Objective: Tuberous sclerosis complex (TSC) is a genetic disorder, characterized by tumor formation in the brain and other organs, and severe neurological symptoms, such as epilepsy. Abnormal vascular endothelial growth factor (VEGF) expression may ... ...

Abstract	Objective: Tuberous sclerosis complex (TSC) is a genetic disorder, characterized by tumor formation in the brain and other organs, and severe neurological symptoms, such as epilepsy. Abnormal vascular endothelial growth factor (VEGF) expression may promote angiogenesis in kidney and lung tumors in TSC and has been identified in brain specimens from TSC patients, but the role of VEGF and vascular abnormalities in neurological manifestations of TSC is poorly defined. In this study, we investigated abnormalities in brain VEGF expression, cerebral blood vessel anatomy, and blood-brain barrier (BBB) structure and function in a mouse model of TSC. Methods: Tsc1 Results: VEGF expression was elevated in cortex of Tsc1 Significance: Increased brain VEGF expression is dependent on mTOR pathway activation and promotes cerebral vascular abnormalities and increased BBB permeability in a mouse model of TSC. BBB modulation may affect epileptogenesis and represent a rational treatment for epilepsy in TSC.
MeSH term(s)	Humans ; Mice ; Animals ; Blood-Brain Barrier ; Vascular Endothelial Growth Factor A/metabolism ; Tuberous Sclerosis/complications ; Tuberous Sclerosis/genetics ; Tumor Suppressor Proteins/genetics ; Tuberous Sclerosis Complex 1 Protein/genetics ; Tuberous Sclerosis Complex 1 Protein/metabolism ; Epilepsy/genetics ; Epilepsy/metabolism ; Seizures ; TOR Serine-Threonine Kinases/genetics ; Sirolimus ; Receptors, Vascular Endothelial Growth Factor/metabolism
Chemical Substances	Vascular Endothelial Growth Factor A ; Tumor Suppressor Proteins ; Tuberous Sclerosis Complex 1 Protein ; TOR Serine-Threonine Kinases (EC 2.7.11.1) ; Sirolimus (W36ZG6FT64) ; Receptors, Vascular Endothelial Growth Factor (EC 2.7.10.1)
Language	English
Publishing date	2023-12-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	216382-2
ISSN	1528-1167 ; 0013-9580
ISSN (online)	1528-1167
ISSN	0013-9580
DOI	10.1111/epi.17848
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Zs.A 517: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 475: Show issues

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Article: Periodic and aperiodic changes to cortical EEG in response to pharmacological manipulation.

Salvatore, Sofia V / Lambert, Peter M / Benz, Ann / Rensing, Nicholas R / Wong, Michael / Zorumski, Charles F / Mennerick, Steven

bioRxiv : the preprint server for biology

2023

Abstract: Cortical electroencephalograms (EEG) may help understanding of neuropsychiatric illness and new treatment mechanisms. The aperiodic component (1/ : Significance statebment: Neuropsychiatric illness is widely prevalent and debilitating. Causes are not ... ...

Abstract	Cortical electroencephalograms (EEG) may help understanding of neuropsychiatric illness and new treatment mechanisms. The aperiodic component (1/ Significance statebment: Neuropsychiatric illness is widely prevalent and debilitating. Causes are not well understood, but some hypotheses point toward altered excitation/inhibition (E/I) balance. Here, we use cortical electroencephalograms (EEG) in mice, given applicability of cortical EEG across species, and evaluate the impact of validated drugs, including anxiolytics (pentobarbital and diazepam), along with novel rapid-acting antidepressants (ketamine and allopregnanolone). We focus on analyzing the aperiodic component of EEG power spectra, which may be associated with changes in E/I ratio. We show that aperiodic exponent of EEG power spectra is not a reliable marker of E/I ratio. Moreover, the concept of E/I ratio may be too broad and complex to be defined by an EEG parameter.
Language	English
Publishing date	2023-09-22
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.09.21.558828
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Article: A role for δ subunit-containing GABA

Lambert, Peter M / Salvatore, Sofia V / Lu, Xinguo / Shu, Hong-Jin / Benz, Ann / Rensing, Nicholas / Yuede, Carla M / Wong, Michael / Zorumski, Charles F / Mennerick, Steven

bioRxiv : the preprint server for biology

2024

Abstract: GABA : Significance statement: The impact on cortical EEG of inhibition on PV+ neurons was studied by deleting a ... ...

Abstract	GABA Significance statement: The impact on cortical EEG of inhibition on PV+ neurons was studied by deleting a GABA
Language	English
Publishing date	2024-03-29
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.25.586604
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Article: GABAergic interneurons contribute to the fatal seizure phenotype of CLN2 disease mice.

Takahashi, Keigo / Rensing, Nicholas R / Eultgen, Elizabeth M / Wang, Sophie H / Nelvagal, Hemanth R / Le, Steven Q / Roberts, Marie S / Doray, Balraj / Han, Edward B / Dickson, Patricia I / Wong, Michael / Sands, Mark S / Cooper, Jonathan D

bioRxiv : the preprint server for biology

2024

Abstract: GABAergic interneuron deficits have been implicated in the epileptogenesis of multiple neurological diseases. While epileptic seizures are a key clinical hallmark of CLN2 disease, a childhood-onset neurodegenerative lysosomal storage disorder caused by a ...

Abstract	GABAergic interneuron deficits have been implicated in the epileptogenesis of multiple neurological diseases. While epileptic seizures are a key clinical hallmark of CLN2 disease, a childhood-onset neurodegenerative lysosomal storage disorder caused by a deficiency of tripeptidyl peptidase 1 (TPP1), the etiology of these seizures remains elusive. Given that
Language	English
Publishing date	2024-03-30
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.03.29.587276
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Article: Threading the Needle: Intrapelvic Displacement of a Femoral Neck Fracture through the Obturator Foramen.

Prabhakar, Gautham / Kusnezov, Nicholas / Rensing, Nicholas / Abdelgawad, Amr

Case reports in orthopedics

2018 Volume 2018, Page(s) 2506187

Abstract: Despite timely and appropriate management, displaced femoral neck fractures are often devastating injuries for the young patient. The risk of negative sequelae is further amplified with increasing displacement and vertical fracture patterns. Open ... ...

Abstract	Despite timely and appropriate management, displaced femoral neck fractures are often devastating injuries for the young patient. The risk of negative sequelae is further amplified with increasing displacement and vertical fracture patterns. Open anatomic reduction with rigid internal fixation is essential to maximize the healing potential in displaced fractures of the femoral neck. Successful primary osteosynthesis of significantly displaced femoral neck fractures in the young patient has been reported in the literature. We present a unique case of open reduction and internal fixation of a high-energy femoral neck fracture with extrusion of the head through the obturator foramen into the pelvis without associated acetabular or pelvic injury.
Language	English
Publishing date	2018-04-01
Publishing country	United States
Document type	Case Reports
ZDB-ID	2684648-2
ISSN	2090-6757 ; 2090-6749
ISSN (online)	2090-6757
ISSN	2090-6749
DOI	10.1155/2018/2506187
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Article ; Online: Functional neuropathology of neonatal hypoxia-ischemia by single-mouse longitudinal electroencephalography.

Johnson, Kevin J / Moy, Brianna / Rensing, Nicholas / Robinson, Alexia / Ly, Michael / Chengalvala, Ramya / Wong, Michael / Galindo, Rafael

Epilepsia

2022 Volume 63, Issue 12, Page(s) 3037–3050

Abstract: Objective: Neonatal cerebral hypoxia-ischemia (HI) results in symptomatic seizures and long-term neurodevelopmental disability. The Rice-Vannucci model of rodent neonatal HI has been used extensively to examine and translate the functional consequences ... ...

Abstract	Objective: Neonatal cerebral hypoxia-ischemia (HI) results in symptomatic seizures and long-term neurodevelopmental disability. The Rice-Vannucci model of rodent neonatal HI has been used extensively to examine and translate the functional consequences of acute and chronic HI-induced encephalopathy. Yet, longitudinal electrophysiological characterization of this brain injury model has been limited by the size of the neonatal mouse's head and postnatal maternal dependency. We overcome this challenge by employing a novel method of longitudinal single-mouse electroencephalography (EEG) using chronically implanted subcranial electrodes in the term-equivalent mouse pup. We characterize the neurophysiological disturbances occurring during awake and sleep states in the acute and chronic phases following newborn brain injury. Methods: C57BL/6 mice underwent long-term bilateral subcranial EEG and electromyographic electrode placement at postnatal day 9 followed by unilateral carotid cauterization and exposure to 40 minutes of hypoxia the following day. EEG recordings were obtained prior, during, and intermittently after the HI procedure from postnatal day 10 to weaning age. Quantitative EEG and fast Fourier transform analysis were used to evaluate seizures, cortical cerebral dysfunction, and disturbances in vigilance states. Results: We observed neonatal HI-provoked electrographic focal and bilateral seizures during or immediately following global hypoxia and most commonly contralateral to the ischemic injury. Spontaneous chronic seizures were not seen. Injured mice developed long-term asymmetric EEG background attenuation in all frequencies and most prominently during non-rapid eye movement (NREM) sleep. HI mice also showed transient impairments in vigilance state duration and transitions during the first 2 days following injury. Significance: The functional burden of mouse neonatal HI recorded by EEG resembles closely that of the injured human newborn. The use of single-mouse longitudinal EEG in this immature model can advance our understanding of the developmental and pathophysiological mechanisms of neonatal cerebral injury and help translate novel therapeutic strategies against this devastating condition.
MeSH term(s)	Humans ; Mice ; Animals ; Mice, Inbred C57BL ; Ischemia ; Seizures/etiology ; Brain Injuries ; Hypoxia
Language	English
Publishing date	2022-10-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	216382-2
ISSN	1528-1167 ; 0013-9580
ISSN (online)	1528-1167
ISSN	0013-9580
DOI	10.1111/epi.17403
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Zs.A 517: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Non-sedative cortical EEG signatures of allopregnanolone and functional comparators.

Lambert, Peter M / Ni, Richard / Benz, Ann / Rensing, Nicholas R / Wong, Michael / Zorumski, Charles F / Mennerick, Steven

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

2022 Volume 48, Issue 2, Page(s) 371–379

Abstract: Neurosteroids that positively modulate ... ...

Abstract	Neurosteroids that positively modulate GABA
MeSH term(s)	Humans ; Mice ; Animals ; Pregnanolone/pharmacology ; Ketamine/pharmacology ; Pentobarbital/pharmacology ; Receptors, GABA-A/physiology ; Diazepam/pharmacology ; Neurosteroids ; Antidepressive Agents/pharmacology ; gamma-Aminobutyric Acid ; Electroencephalography
Chemical Substances	Pregnanolone (BXO86P3XXW) ; Ketamine (690G0D6V8H) ; Pentobarbital (I4744080IR) ; Receptors, GABA-A ; Diazepam (Q3JTX2Q7TU) ; Neurosteroids ; Antidepressive Agents ; gamma-Aminobutyric Acid (56-12-2)
Language	English
Publishing date	2022-09-27
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	639471-1
ISSN	1740-634X ; 0893-133X
ISSN (online)	1740-634X
ISSN	0893-133X
DOI	10.1038/s41386-022-01450-x
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