The presence of dysmorphic neurons with strong cytoplasmatic accumulation of heavy non‐phosphorylated neurofilament is crucial for the diagnostics of focal cortical dysplasia type II (FCDII). While ...ILAE's classification describes neocortical dysplasias, some groups have reported patients with mesial t abnormal neurons in the hippocampus of mesial temporal lobe epilepsy. Here we report a patient with such abnormal neurons in the hippocampus and compared it with previous reports of hippocampal dysplasia. Finally, we discuss the need for diagnostic criteria of hippocampal dysplasia.
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Objective
Drebrins are crucial for synaptic function and dendritic spine development, remodeling, and maintenance. In temporal lobe epilepsy (TLE) patients, a significant hippocampal synaptic ...reorganization occurs, and synaptic reorganization has been associated with hippocampal hyperexcitability. This study aimed to evaluate, in TLE patients, the hippocampal expression of drebrin using immunohistochemistry with DAS2 or M2F6 antibodies that recognize adult (drebrin A) or adult and embryonic (pan‐drebrin) isoforms, respectively.
Methods
Hippocampal sections from drug‐resistant TLE patients with hippocampal sclerosis (HS; TLE, n = 33), of whom 31 presented with type 1 HS and two with type 2 HS, and autopsy control cases (n = 20) were assayed by immunohistochemistry and evaluated for neuron density, and drebrin A and pan‐drebrin expression. Double‐labeling immunofluorescences were performed to localize drebrin A–positive spines in dendrites (MAP2), and to evaluate whether drebrin colocalizes with inhibitory (GAD65) and excitatory (VGlut1) presynaptic markers.
Results
Compared to controls, TLE patients had increased pan‐drebrin in all hippocampal subfields and increased drebrin A–immunopositive area in all hippocampal subfields but CA1. Drebrin‐positive spine density followed the same pattern as total drebrin quantification. Confocal microscopy indicated juxtaposition of drebrin‐positive spines with VGlut1‐positive puncta, but not with GAD65‐positive puncta. Drebrin expression in the dentate gyrus of TLE cases was associated negatively with seizure frequency and positively with verbal memory. TLE patients with lower drebrin‐immunopositive area in inner molecular layer (IML) than in outer molecular layer (OML) had a lower seizure frequency than those with higher or comparable drebrin‐immunopositive area in IML compared with OML.
Significance
Our results suggest that changes in drebrin‐positive spines and drebrin expression in the dentate gyrus of TLE patients are associated with lower seizure frequency, more preserved verbal memory, and a better postsurgical outcome.
Summary
Objective
Increased T2 relaxation time is often seen in temporal lobe epilepsy (TLE) with hippocampal sclerosis. Water content directly affects the effective T2 in a voxel. Our aim was to ...evaluate the relation between T2 values and two molecules associated with brain water homeostasis aquaporin 4 (AQP4) and chondroitin sulfate proteoglycan (CSPG), as well as cellular populations in the hippocampal region of patients with TLE.
Methods
Hippocampal T2 imaging and diffusion tensor imaging (DTI) were obtained from 42 drug‐resistant patients with TLE and 20 healthy volunteers (radiologic controls, RCs). A similar protocol (ex vivo) was applied to hippocampal sections from the same TLE cases and 14 autopsy control hippocampi (histologic and radiologic controls, HRCs), and each hippocampal subfield was evaluated. Hippocampal sections from TLE cases and HRC controls were submitted to immunohistochemistry for neurons (neuron nuclei NeuN), reactive astrocytes (glial fibrillary acidic protein GFAP), activated microglia (human leukocyte antigen‐D–related HLA‐DR), polarized AQP4, and CSPG.
Results
Patients with TLE had higher in vivo and ex vivo hippocampal T2 relaxation time. Hippocampi from epilepsy cases had lower neuron density, higher gliosis, decreased AQP4 polarization, and increased CSPG immunoreactive area. In vivo relaxation correlated with astrogliosis in the subiculum and extracellular CSPG in the hilus. Ex vivo T2 relaxation time correlated with astrogliosis in the hilus, CA4, and subiculum, and with microgliosis in CA1. The difference between in vivo and ex vivo relaxation ratio correlated with mean diffusivity and with the immunopositive area for CSPG in the hilus.
Significance
Our data indicate that astrogliosis, microgliosis, and CSPG expression correlate with the increased T2 relaxation time seen in the hippocampi of patients with TLE.
The kallikrein-kinin system is a versatile regulatory network implicated in various biological processes encompassing inflammation, nociception, blood pressure control, and central nervous system ...functions. Its physiological impact is mediated through G-protein-coupled transmembrane receptors, specifically the B1 and B2 receptors. Dopamine, a key catecholamine neurotransmitter widely distributed in the CNS, plays a crucial role in diverse physiological functions including motricity, reward, anxiety, fear, feeding, sleep, and arousal. Notably, the potential physical interaction between bradykinin and dopaminergic receptors has been previously documented. In this study, we aimed to explore whether B2R modulation in catecholaminergic neurons influences the dopaminergic pathway, impacting behavioral, metabolic, and motor aspects in both male and female mice. B2R ablation in tyrosine hydroxylase cells reduced the body weight and lean mass without affecting body adiposity, substrate oxidation, locomotor activity, glucose tolerance, or insulin sensitivity in mice. Moreover, a B2R deficiency in TH cells did not alter anxiety levels, exercise performance, or motor coordination in female and male mice. The concentrations of monoamines and their metabolites in the substantia nigra and cortex region were not affected in knockout mice. In essence, B2R deletion in TH cells selectively influenced the body weight and composition, leaving the behavioral and motor aspects largely unaffected.
Highlights • Cannabidiol into prefrontal cortex impaired fear memory consolidation only when it occurred at 5 h after conditioning. • Cannabidiol decreases dopamine release in prefrontal cortex ...following memory retrieval 5 days after training. • Post-training infusion of cannabidiol reduces genes expression in cortico-limbic circuits following memory retrieval.
Summary
Objective
Hippocampal sclerosis is a common finding in patients with temporal lobe epilepsy (TLE), and magnetic resonance imaging (MRI) studies associate the reduction of hippocampal volume ...with the neuron loss seen on histologic evaluation. Astrogliosis and increased levels of chondroitin sulfate, a major component of brain extracellular matrix, are also seen in hippocampal sclerosis. Our aim was to evaluate the association between hippocampal volume and chondroitin sulfate, as well as neuronal and astroglial populations in the hippocampus of patients with TLE.
Methods
Patients with drug‐resistant TLE were subdivided, according to hippocampal volume measured by MRI, into two groups: hippocampal atrophy (HA) or normal volume (NV) cases. Hippocampi from TLE patients and age‐matched controls were submitted to immunohistochemistry to evaluate neuronal population, astroglial population, and chondroitin sulfate expression with antibodies against neuron nuclei protein (NeuN), glial fibrillary acidic protein (GFAP), and chondroitin sulfate (CS‐56) antigens, respectively.
Results
Both TLE groups were clinically similar. NV cases had higher hippocampal volume, both ipsilateral and contralateral, when compared to HA. Compared to controls, NV and HA patients had reduced neuron density, and increased GFAP and CS‐56 immunopositive area. There was no statistical difference between NV and HA groups in neuron density or immunopositive areas for GFAP and CS‐56. Hippocampal volume correlated positively with neuron density in CA1 and prosubiculum, and with immunopositive areas for CS‐56 in CA1, and negatively with immunopositive area for GFAP in CA1. Multiple linear regression analysis indicated that both neuron density and CS‐56 immunopositive area in CA1 were statistically significant predictors of hippocampal volume.
Significance
Our findings indicate that neuron density and chondroitin sulfate immunopositive area in the CA1 subfield are crucial for the hippocampal volume, and that chondroitin sulfate is important for the maintenance of a normal hippocampal volume in some cases with severe neuron loss.
N-methyl-D-aspartate receptor (NMDAr) antagonists such as ketamine (KET) produce psychotic-like behavior in both humans and animal models. NMDAr hypofunction affects normal oscillatory dynamics and ...synaptic plasticity in key brain regions related to schizophrenia, particularly in the hippocampus and the prefrontal cortex. It has been shown that prior long-term potentiation (LTP) occluded the increase of synaptic efficacy in the hippocampus-prefrontal cortex pathway induced by MK-801, a non-competitive NMDAr antagonist. However, it is not clear whether LTP could also modulate aberrant oscillations and short-term plasticity disruptions induced by NMDAr antagonists. Thus, we tested whether LTP could mitigate the electrophysiological changes promoted by KET. We recorded HPC-PFC local field potentials and evoked responses in urethane anesthetized rats, before and after KET administration, preceded or not by LTP induction. Our results show that KET promotes an aberrant delta-high-gamma cross-frequency coupling in the PFC and an enhancement in HPC-PFC evoked responses. LTP induction prior to KET attenuates changes in synaptic efficiency and prevents the increase in cortical gamma amplitude comodulation. These findings are consistent with evidence that increased efficiency of glutamatergic receptors attenuates cognitive impairment in animal models of psychosis. Therefore, high-frequency stimulation in HPC may be a useful tool to better understand how to prevent NMDAr hypofunction effects on synaptic plasticity and oscillatory coordination in cortico-limbic circuits.
Brain disturbances during development can have a lasting impact on neural function and behavior. Seizures during this critical period are linked to significant long-term consequences such as ...neurodevelopmental disorders, cognitive impairments, and psychiatric symptoms, resulting in a complex spectrum of multimorbidity. The hippocampus-prefrontal cortex (HPC-PFC) circuit emerges as a potential common link between such disorders. However, the mechanisms underlying these outcomes and how they relate to specific behavioral alterations are unclear. We hypothesized that specific dysfunctions of hippocampal-cortical communication due to early-life seizure would be associated with distinct behavioral alterations observed in adulthood. Here, we performed a multilevel study to investigate behavioral, electrophysiological, histopathological, and neurochemical long-term consequences of early-life
in male rats. We show that adult animals submitted to early-life seizure (ELS) present working memory impairments and sensorimotor disturbances, such as hyperlocomotion, poor sensorimotor gating, and sensitivity to psychostimulants despite not exhibiting neuronal loss. Surprisingly, cognitive deficits were linked to an aberrant increase in the HPC-PFC long-term potentiation (LTP) in a U-shaped manner, while sensorimotor alterations were associated with heightened neuroinflammation, as verified by glial fibrillary acidic protein (GFAP) expression, and altered dopamine neurotransmission. Furthermore, ELS rats displayed impaired HPC-PFC theta-gamma coordination and an abnormal brain state during active behavior resembling rapid eye movement (REM) sleep oscillatory dynamics. Our results point to impaired HPC-PFC functional connectivity as a possible pathophysiological mechanism by which ELS can cause cognitive deficits and psychiatric-like manifestations even without neuronal loss, bearing translational implications for understanding the spectrum of multidimensional developmental disorders linked to early-life seizures.
...a Canadian-based study showed a 35% lifetime prevalence of mental health in persons with epilepsy compared to 20.7% in the average population (Tellez-Zenteno et al., 2007). Kanner and Michaelis et ...al. clinical papers emphasize the urgent need for integrated mental health care to improve quality of life and decrease mortality in persons with epilepsy. The authors also analyzed other potential factors associated with TLE comorbidities, including genes widely explored in psychiatry and epileptology (Hu and Russek, 2008; Esmail et al., 2015), and could shed light on specific differences between types of psychiatric comorbidity. Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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