The interaction between cannabinoids and long-term synaptic plasticity: A survey on memory formation and underlying mechanisms.

Synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), is an essential phenomenon in memory formation as well as maintenance along with many other cognitive functions, such as those needed for coping with external stimuli. Synaptic plasticity consists of gradual changes in the biochemistry and morphology of pre- and postsynaptic neurons, particularly in the hippocampus. Consuming marijuana as a primary source of exocannabinoids immediately impairs attention and working memory-related tasks. Evidence regarding the effects of cannabinoids on LTP and memory is contradictory. While cannabinoids can affect a variety of specific cannabinoid receptors (CBRs) and nonspecific receptors throughout the body and brain, they exert miscellaneous systemic and local cerebral effects. Given the increasing use of cannabis, mainly among the young population, plus its potential adverse long-term effects on learning and memory processes, it could be a future global health challenge. Indeed, the impact of cannabinoids on memory is multifactorial and depends on the dosage, timing, formula, and route of consumption, plus the background complex interaction of the endocannabinoids system with other cerebral networks. Herein, we review how exogenously administrated organic cannabinoids, CBRs agonists or antagonists, and endocannabinoids can affect LTP and synaptic plasticity through various receptors in interaction with other cerebral pathways and primary neurotransmitters.

Revisiting characteristics of oncogenic extrachromosomal DNA as mobile enhancers on neuroblastoma and glioma cancers.

Cancer can be induced by a variety of possible causes, including tumor suppressor gene failure and proto-oncogene hyperactivation. Tumor-associated extrachromosomal circular DNA has been proposed to endanger human health and speed up the progression of cancer. The amplification of ecDNA has raised the oncogene copy number in numerous malignancies according to whole-genome sequencing on distinct cancer types. The unusual structure and function of ecDNA, and its potential role in understanding current cancer genome maps, make it a hotspot to study tumor pathogenesis and evolution. The discovery of the basic mechanisms of ecDNA in the emergence and growth of malignancies could lead researchers to develop new cancer therapies. Despite recent progress, different aspects of ecDNA require more investigation. We focused on the features, and analyzed the bio-genesis, and origin of ecDNA in this review, as well as its functions in neuroblastoma and glioma cancers.

MicroRNA alterations in neuropathologic cognitive disorders with an emphasis on dementia: Lessons from animal models.

Cognitive dysfunction is a state of losing or having difficulties in remembering, learning, focusing, or making decisions that impact individual healthy life. Small single-stranded and nonprotein coding RNAs, microRNAs (miRNAs) participate actively in regulatory processes, incorporate cognitive signaling pathways, and intensely affect cognitive evolution. miRNAs exert their modification activities through translational or transcriptional processes. Reportedly, cognitive impairment and dementia are rising, especially in developing countries. Herein we provided a brief review of original studies addressing miRNA changes in the most common neurological diseases with a focus on dementia and Alzheimer's disease. It must be noted that an increase in the level of certain miRNAs but a decrease in other ones deteriorate cognitive performance. The current review revealed that induction of miR-214-3p, miR-302, miR-21, miR- 200b/c, miR-207, miR-132, miR-188-3p and 5p, and miR-873 improved cognitive impairment in various cognitive tasks. On the other hand, intentionally lowering the level of miR-34a, miR-124, miR-574, and miR-191a enhanced cognitive function and memory. Synaptic dysfunction is a core cause of cognitive dysfunction; miRNA-34, miRNA-34-c, miRNA-124, miRNA-188-5p, miRNA-210-5p, miRNA-335-3p, and miRNA-134 strongly influence synaptic-related mechanisms. The downregulation of miRNA-132 aggregates both amyloid and tau in tauopathy. Concerning the massive burden of neurological diseases worldwide, the future challenge is the translation of animal model knowledge into the detection of pathophysiological stages of neurocognitive disorders and designing efficient therapeutic strategies. While the delivery procedure of agomir or antagomir miRNAs into the brain is invasive and only applied in animal studies, finding a safe and specific delivery route is a priority.

Evaluation of the neuroprotective effects of Vitamin E on the rat substantia nigra neural cells exposed to electromagnetic field: An ultrastructural study.

Electromagnetic fields (EMFs) could induce oxidative stress (OS) in human tissues. Lipid peroxidation (LPO) is the main hallmark of OS that harms neural cell components, primarily lipids in the myelin sheaths and membranes. Vitamin E is a lipophilic antioxidant that protects cells from OS-related damages and inhibits the LPO process. In this study, male rats were assigned into three groups of Control, EMF, and EMF+ Vitamin E. The EMF producer equipment produced an alternate current of 50 Hz, 3 Mili Tesla (mT). At the end of the experiment, half of the substantia nigra in every sample was used for measurement of the malondialdehyde (MDA) level as the end-product of the LPO and activity of superoxide dismutase (SOD) enzyme. The next half of the tissue was prepared for transmission electron microscopy (TEM). In the EMF group, MDA level was enhanced and SOD value decreased significantly compared to the control group, but Vitamin E could restore these changes. In rats undergone EMF, heterochromatic nucleus and destruction in some portions of the nuclear membrane were detected. The segmental separation or destruction of myelin sheath lamellae was observed in nerve fibers. In treated animals, the nucleus was round, less heterochromatic, with a regular membrane. Separation of myelin sheath lamellae in some nerve fibers was slighter than the radiation group. Considering the results, EMF exposure induces LPO and triggers ultrastructural changes in the cell membranes, nucleus, and myelin sheath of substantia nigra cells, but Vitamin E consumption weakens these neuropathological alterations.

A potential entanglement between the spinal cord and hippocampus: Theta rhythm correlates with neurogenesis deficiency following spinal cord injury in male rats.

Cognitive deficits due to spinal cord injury (SCI) have been elucidated in both animals and humans with SCI. Such disorders may cause concomitant oscillatory changes in regions of the brain involving in cognition; a subject that has not been directed mechanistically. One of the crucial oscillations, having a prominent role in cognition, particularly spatial memory, is hippocampal theta rhythm. Our research revealed that SCI could induce changes not only in the neurogenesis and apoptosis rate of the hippocampus but also in theta power as well as receptors involving in the generation of this rhythm. Herein we used 24 male Wistar rats (Sham/SCI = 12) and examined the effect of spinal cord contusion on hippocampal theta rhythm, spatial memory, and neurodegeneration. We proved that SCI eliminates hippocampus-dependent theta power through spatial working memory, and correlates significantly with neurodegeneration and expression of receptors (NMDA, GABAA, Muscarinic1/M1), which are in turn essential in generation of theta rhythm. The immunohistochemistry analysis also demonstrated a significant decrease in DCX+ and BrdU+ cells; however, according to TUNEL assay, apoptosis is significantly higher in SCI-induced animals. The western blotting analysis further showed a significant reduction of the abovementioned receptors in the hippocampus. We also verified that SCI impairs the spatial memory, proved by poor performance in the Y-maze task. As well as, based on the local field potential recordings analysis, SCI decreases the power of theta rhythm. Eventually, this study demonstrated that chronic brain neurodegeneration occurs after SCI accompanied by theta rhythm and cognitive deficiency.

Combination of curcumin with autologous transplantation of adult neural stem/progenitor cells leads to more efficient repair of damaged cerebral tissue of rat.

NEW FINDINGS: What is the central question of this study? Can the neuroprotective agent curcumin affect restorative action of neural stem/progenitor cells in the injured rat brain? What is the main finding and its importance? In the presence of curcumin, transplantation of neural stem/progenitor cells in the context of PuraMatrix reduced lesion size and reactive inflammatory responses, and boosted survival rate of grafted neurons. In addition it improved the neurological status of injured animals. This could be beneficial in designing new therapeutic approaches for brain injury based on this combination therapy. ABSTRACT: Traumatic brain injury (TBI) is catastrophic neurological damage associated with substantial morbidity and mortality. To date, there is no specific treatment for restoring lost brain tissue. In light of the complex pathology of brain injury, the present study evaluated the effects of combination therapy using autologous neural stem/progenitor cells (NS/PCs), PuraMatrix (PM) and curcumin in an animal model of brain injury. After stereotactic biopsy of subventricular zone tissue and culture of NS/PCs, 36 male Wistar rats (150-200 g) were randomly divided into six groups receiving dimethyl sulfoxide (DMSO),  curcumin (100 mg kg-1 in DMSO), PM + curcumin (100 mg kg-1 in DMSO), NS/PCs + curcumin (100 mg kg-1 in DMSO), NS/PCs + PM + curcumin (100 mg kg-1 in DMSO) and NS/PCs + PM + curcumin (1 µm) following acute brain injury. The animals were evaluated in term of neurological status for 4 weeks, then decapitated. Nissl and TUNEL staining and immunohistochemistry for bromodeoxyuridine, glial fibrillary acidic protein, doublecortin, Map2, Olig2, Iba1 and CD68 were performed. We found that combination therapy by NS/PCs + PM + curcumin reduced the lesion size, astrogliosis, macrophage and microglial reaction as well as the number of apoptotic cells. Moreover, the transplanted cells were able to survive and differentiate after 4 weeks. Besides these findings, transplantation of NS/PCs in the context of PM and curcumin improved the neurological status of injured animals. In conclusion, our data suggest that this combination therapy can be beneficial in developing future therapeutic approaches for brain injury.

Effect of castration on the susceptibility of male rats to the sleep deprivation-induced impairment of behavioral and synaptic plasticity.

In both human and animal studies, the effect of sleep deficiency on cognitive performances has mostly been studied during adulthood in males, but very little data exist concerning the effects of poor sleep in gonadal hormones-depleted status, such as aging or gonadectomized (GDX) male animal models. The present study investigated the potential modulatory effects of the endogenous male sex hormones on the 48h REM sleep deprivation (SD)-induced cognitive and synaptic impairments by comparing the gonadally intact with castrated male rats, a rodent model of androgen-deprived male animals. The multiple platform method was used for inducing REM-SD and spatial performances were evaluated using Morris water maze (MWM) task. Early long-term potentiation (E-LTP) was measured in area CA1 of the hippocampus and PCR and western blotting assays were employed to assess brain derived neurotrophic factor (BDNF) gene and protein expression in the hippocampus. To reveal any influence of sleep loss on stress level, we also evaluated the plasma corticosterone levels of animals. Regardless of reproductive status, REM-SD significantly disrupted short-term memory and LTP, as well as hippocampal BDNF expression. The corticosterone levels were not significantly changed following REM-SD neither in intact nor in GDX male rats. These findings suggest that depletion of male sex steroid hormones by castration does not lead to any heightened sensitivity of male animals to the deleterious effects of 48h REM-SD on cognitive and synaptic performances.

Effects of TRPV1 on the hippocampal synaptic plasticity in the epileptic rat brain.

Temporal lobe epilepsy is often presented by medically intractable recurrent seizures due to dysfunction of temporal lobe structures, mostly the temporomesial structures. The role of transient receptor potential vaniloid 1 (TRPV1) activity on synaptic plasticity of the epileptic brain tissues was investigated. We studied hippocampal TRPV1 protein content and distribution in the hippocampus of epileptic rats. Furthermore, the effects of pharmacologic modulation of TRPV1 receptors on field excitatory postsynaptic potentials have been analyzed after induction of long term potentiation (LTP) in the hippocampal CA1 and CA3 areas after 1 day (acute phase) and 3 months (chronic phase) of pilocarpine-induced status epilepticus (SE). A higher expression of TRPV1 protein in the hippocampus as well as a higher distribution of this channel in CA1 and CA3 areas in both acute and chronic phases of pilocarpine-induced SE was observed. Activation of TRPV1 using capsaicin (1 µM) enhanced LTP induction in CA1 region in non-epileptic rats. Inhibition of TRPV1 by capsazepine (10 µM) did not affect LTP induction in non-epileptic rats. In acute phase of SE, activation of TRPV1 enhanced LTP in both CA1 and CA3 areas but TRPV1 inhibition did not affect LTP. In chronic phase of SE, application of TRPV1 antagonist enhanced LTP induction in CA1 and CA3 regions but TRPV1 activation had no effect on LTP. These findings indicate that a higher expression of TRPV1 in epileptic conditions is accompanied by a functional impact on the synaptic plasticity in the hippocampus. This suggests TRPV1 as a potential target in treatment of seizure attacks.

A new insight into the role of pericytes in ischemic stroke.

The functional structure of the blood-brain barrier (BBB) deteriorates after stroke by developing diffuse microvascular and neurovascular dysfunction and loss of white matter integrity. This causes nervous tissue injury and causes sensory and motor disabilities in stroke patients. Improving the integrity of the BBB and neurovascular remodeling after stroke can promote post-stroke injury conditions. Pericytes are contractile cells abundant in the BBB and sandwiched between astrocytes and endothelial cells of the microvessels. Stroke could lead to the degeneration of pericytes in the BBB. However, recent evidence shows that promoting pericytes enhances BBB integrity and neurovascular remodeling. Furthermore, pericytes achieve multipotent properties under hypoxic conditions, allowing them to transdifferentiate into the brain resident cells such as microglia. Microglia regulate immunity and inflammatory response after stroke. The current review studies recent findings in the intervening mechanisms underlying the regulatory effect of pericytes in BBB recovery after stroke.

Targeted gene delivery to the brain using CDX-modified chitosan nanoparticles.

Introduction: Blood-brain barrier with strictly controlled activity participates in a coordinated transfer of bioactive molecules from the blood to the brain. Among different delivery approaches, gene delivery is touted as a promising strategy for the treatment of several nervous system disorders. The transfer of exogenous genetic elements is limited by the paucity of suitable carriers. As a correlate, designing high-efficiency biocarriers for gene delivery is challenging. This study aimed to deliver pEGFP-N1 plasmid into the brain parenchyma using CDX-modified chitosan (CS) nanoparticles (NPs). Methods: Herein, we attached CDX, a 16 amino acids peptide, to the CS polymer using bifunctional polyethylene glycol (PEG) formulated with sodium tripolyphosphate (TPP), by ionic gelation method. Developed NPs and their nanocomplexes with pEGFP-N1 (CS-PEG-CDX/pEGFP) were characterized using DLS, NMR, FTIR, and TEM analyses. For in vitro assays, a rat C6 glioma cell line was used for cell internalization efficiency. The biodistribution and brain localization of nanocomplexes were studied in a mouse model after intraperitoneal injection using in vivo imaging and fluorescent microscopy. Results: Our results showed that CS-PEG-CDX/pEGFP NPs were uptaken by glioma cells in a dose-dependent manner. In vivo imaging revealed successful entry into the brain parenchyma indicated with the expression of green fluorescent protein (GFP) as a reporter protein. However, the biodistribution of developed NPs was also evident in other organs especially the spleen, liver, heart, and kidneys. Conclusion: Based on our results, CS-PEG-CDX NPs can provide a safe and effective nanocarrier for brain gene delivery into the central nervous system (CNS).

CDX-modified chitosan nanoparticles remarkably reduce therapeutic dose of fingolimod in the EAE model of mice.

Fingolimod (Fin), an FDA-approved drug, is used to control relapsing-remitting multiple sclerosis (MS). This therapeutic agent faces crucial drawbacks like poor bioavailability rate, risk of cardiotoxicity, potent immunosuppressive effects, and high cost. Here, we aimed to assess the therapeutic efficacy of nano-formulated Fin in a mouse model of experimental autoimmune encephalomyelitis (EAE). Results showed the suitability of the present protocol in the synthesis of Fin-loaded CDX-modified chitosan (CS) nanoparticles (NPs) (Fin@CSCDX) with suitable physicochemical features. Confocal microscopy confirmed the appropriate accumulation of synthesized NPs within the brain parenchyma. Compared to the control EAE mice, INF-γ levels were significantly reduced in the group that received Fin@CSCDX (p < 0.05). Along with these data, Fin@CSCDX reduced the expression of TBX21, GATA3, FOXP3, and Rorc associated with the auto-reactivation of T cells (p < 0.05). Histological examination indicated a low-rate lymphocyte infiltration into the spinal cord parenchyma after the administration of Fin@CSCDX. Of note, HPLC data revealed that the concentration of nano-formulated Fin was about 15-fold less than Fin therapeutic doses (TD) with similar reparative effects. Neurological scores were similar in both groups that received nano-formulated fingolimod 1/15th of free Fin therapeutic amounts. Fluorescence imaging indicated that macrophages and especially microglia can efficiently uptake Fin@CSCDX NPs, leading to the regulation of pro-inflammatory responses. Taken together, current results indicated that CDX-modified CS NPs provide a suitable platform not only for the efficient reduction of Fin TD but also these NPs can target the brain immune cells during neurodegenerative disorders.

Transplantation of bioengineered Reelin-loaded PLGA/PEG micelles can accelerate neural tissue regeneration in photothrombotic stroke model of mouse.

Ischemic stroke is characterized by extensive neuronal loss, glial scar formation, neural tissue degeneration that leading to profound changes in the extracellular matrix, neuronal circuitry, and long-lasting functional disabilities. Although transplanted neural stem cells (NSCs) can recover some of the functional deficit after stroke, retrieval is not complete and repair of lost tissue is negligible. Therefore, the current challenge is to use the combination of NSCs with suitably enriched biomaterials to retain these cells within the infarct cavity and accelerate the formation of a de novo tissue. This study aimed to test the regenerative potential of polylactic-co-glycolic acid-polyethylene glycol (PLGA-PEG) micelle biomaterial enriched with Reelin and embryonic NSCs on photothrombotic stroke model of mice to gain appropriate methods in tissue engineering. For this purpose, two sets of experiments, either in vitro or in vivo models, were performed. In vitro analyses exhibited PLGA-PEG plus Reelin-induced proliferation rate (Ki-67+ NSCs) and neurite outgrowth (axonization and dendritization) compared to PLGA-PEG + NSCs and Reelin + NSCs groups (p < 0.05). Besides, neural differentiation (Map-2+ cells) was high in NSCs cultured in the presence of Reelin-loaded PLGA-PEG micelles (p < 0.05). Double immunofluorescence staining showed that Reelin-loaded PLGA-PEG micelles increased the number of migrating neural progenitor cells (DCX+ cells) and mature neurons (NeuN+ cells) around the lesion site compared to the groups received PLGA-PEG and Reelin alone after 1 month (p < 0.05). Immunohistochemistry results showed that the PLGA/PEG plus Reelin significantly decreased the astrocytic gliosis and increased local angiogenesis (vWF-positive cells) relative to the other groups. These changes led to the reduction of cavity size in the Reelin-loaded PLGA-PEG+NSCs group. Neurobehavioral tests indicated Reelin-loaded PLGA-PEG+NSCs promoted neurological outcome and functional recovery (p < 0.05). These results indicated that Reelin-loaded PLGA-PEG is capable of promoting NSCs dynamic growth, neuronal differentiation, and local angiogenesis following ischemic injury via providing a desirable microenvironment. These features can lead to neural tissue regeneration and functional recovery.

A Review on the Neurological Manifestations of COVID-19 Infection: a Mechanistic View.

There is increasing evidence of neurological manifestations and complications in patients with coronavirus disease 19 (COVID-19). More than one-quarter of patients with COVID-19 developed various neurological symptoms, ranging from headache and dizziness to more serious medical conditions, such as seizures and stroke. The recent investigations introduced hyposmia as a potential early criterion of infection with COVID-19. Despite the high mortality and morbidity rate of COVID-19, its exact mechanism of action and pathogenesis is not well characterized. The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could interact with angiotensin-converting enzyme 2 (ACE2) in the endothelial, neural, and glial cells. In the present study, we reviewed the most common neurological manifestations and complications that emerged after infection with the SARS-CoV-2 and discussed their possible relation to the expression and function of ACE2. Comprehensive and detailed studies are required to uncover how this virus invades the neural system as well as other critical organs.

Modulatory properties of extracellular matrix glycosaminoglycans and proteoglycans on neural stem cells behavior: Highlights on regenerative potential and bioactivity.

Despite the poor regenerative capacity of the adult central nervous system (CNS) in mammals, two distinct regions, subventricular zone (SVZ) and the subgranular zone (SGZ), continue to generate new functional neurons throughout life which integrate into the pre-existing neuronal circuitry. This process is not fixed but highly modulated, revealing many intrinsic and extrinsic mechanisms by which this performance can be optimized for a given environment. The capacity for self-renewal, proliferation, migration, and multi-lineage potency of neural stem cells (NSCs) underlines the necessity of controlling stem cell fate. In this context, the native and local microenvironment plays a critical role, and the application of this highly organized architecture in the CNS has been considered as a fundamental concept in the generation of new effective therapeutic strategies in tissue engineering approaches. The brain extracellular matrix (ECM) is composed of biomacromolecules, including glycosaminoglycans, proteoglycans, and glycoproteins that provide various biological actions through biophysical and biochemical signaling pathways. Herein, we review predominantly the structure and function of the mentioned ECM composition and their regulatory impact on multiple and diversity of biological functions, including neural regeneration, survival, migration, differentiation, and final destiny of NSCs.

Forelimb Motor Skills Deficits Following Thoracic Spinal Cord Injury: Underlying Dopaminergic and Neural Oscillatory Changes in Rat Primary Motor Cortex.

The loss of spinal sensorimotor pathways following spinal cord injury (SCI) can induce retrograde neurodegeneration in the primary motor cortex (M1). However, the effect of thoracic SCI on forelimb motor skills has not been studied clearly. So, herein we aimed to examine the effects of the thoracic SCI model on forelimb motor skills learning, parallel with dopaminergic and oscillatory changes in hindlimb and forelimb areas (HLA and FLA) of M1 in rats. Male Wistar rats were randomly subjected to laminectomy (Control) or contusion SCI at the thoracic (T10) level. Oscillatory activity and motor skills performance were evaluated for six consecutive days using local field potential (LFP) recording and skilled forelimb reaching task, respectively. Dopamine (DA) levels and expression of dopamine receptors (D1R and D2R) were determined in HLA and FLA by ELISA and western blotting. LFP recording results showed a sustained increase of LFP power in SCI rats compared with uninjured rats through skilled reaching training. Also, the SCI group had a lower reaching performance and learning rate in contrast to the Control group. Biochemical analysis of HLA and FLA showed a reduction in DA levels and expression of D1R and D2R after SCI. According to these findings, thoracic SCI causes aberrant changes in the oscillatory activity and dopaminergic system of M1, which are not restricted to HLA but also found in FLA accompanied by a deficit in forelimb motor skills performance.Summary statement: The reorganization of the primary motor cortex, following spinal cord injury, is not restricted to the hind limb area, and interestingly extends to the forelimb limb area, which appears as a dysfunctional change in oscillations and dopaminergic system, associated with a deficit in motor skills learning of forelimb.

Hippocampal neurodegeneration and rhythms mirror each other during acute spinal cord injury in male rats.

Spinal Cord Injury (SCI), triggers neurodegenerative changes in the spinal cord, and simultaneously alters oscillatory manifestations of motor cortex. However, these disturbances may not be limited to motor areas and other parts such as hippocampus, which is vital in the neurogenesis and cognitive function, may be affected in the neurogenic and oscillatory manners. Addressing this remarkable complication of SCI, we evaluated the hippocampal neurogenesis and rhythms through acute phase of SCI. In the present study, we used 40 male rats (Sham.W1 = 10, SCI.W1 = 10, Sham.W2 = 10, SCI.W2 = 10), and findings revealed that contusive SCI declines hippocampal rhythms (Delta, Theta, Beta, Gamma) power and max-frequency. Also, there was a significant decrease in the DCX + and BrdU + cells of the dentate gyrus; correlated significantly with rhythms power decline. Considering the TUNEL assay analysis, there were significantly greater apoptotic cells, in the CA1, CA3, and DG regions of injured animals. Furthermore, according to the western blotting analysis, the expression of receptors (NMDA, GABAA, Muscarinic1), which are essential in the neurogenesis and generation of rhythms significantly attenuated following SCI. Our study demonstrated that acute SCI, alters the power and max-frequency of hippocampal rhythms parallel with changes in the hippocampal neurogenesis, apoptosis, and receptors expression.

Suppression May Improve Adaptation to Worry When Facing Uncertainty: Studying COVID-19 Pandemic.

The COVID-19 pandemic has been associated with increased uncertainty, fear and worry in everyone's life. The effect of changes in daily life has been studied widely, but we do not know how emotion-regulation strategies influence adaptation to a new situation to help them overcome worry in the face of uncertainty. Here, 1,064 self-selected Farsi speaking participants completed an online battery of questionnaires that measured fear of virus and illness, worry, intolerance of uncertainty, and emotion regulation (two subscales: reappraisal, suppression). We also documented the number of daily COVID-19 cases and deaths due to COVID-19 on the day in which participants completed the questionnaire. Our findings suggest a correlation between contamination fear and the number of daily-confirmed cases (r = 0.11), and the number of reported deaths due to COVID-19 (r = 0.09). Worry mediated the relationship between intolerance of uncertainty and fear of virus and illness (b = 0.16, 0.1141 < CI < 0.2113). In addition, suppression moderated the relationship between intolerance of uncertainty and worry (p < 0.01). Our results suggest that suppression (at least in the short term) can be an adaptive response to the worry associated with uncertainty. Suppression can reduce worry, which in turn can decrease fear of contamination and improve adaptation to social distancing requirements. Although, the observed correlations were significant, but considering the sample size, they are not strong, and they should be interpreted cautiously.

Neuronal injury and death following focal mild brain injury: The role of network excitability and seizure.

OBJECTIVES: While traumatic brain injury (TBI) is a predisposing factor for development of post-traumatic epilepsy (PTE), the occurrence of seizures following brain trauma can infuriate adverse consequences of brain injury. However, the effect of seizures in epileptogenesis after mild TBI cannot yet be accurately confirmed. This study was designed to investigate the histopathological and molecular modifications induced by seizures on traumatized brain. MATERIALS AND METHODS: Using a new method, head was traumatized and seizures were evoked by sub-convulsive dose of pentylenetetrazole (PTZ) fifteen days after induction of focal mild TBI. Convulsion assessments were performed one hour after PTZ injection and was followed by histopathological and molecular evaluations. RESULTS: A significantly higher score and longer duration of seizure attacks as well as higher number of epileptiform discharges were observed in the TBI+PTZ group compared to sham and TBI groups. An elevated number of apoptotic cells was observed in the TBI+PTZ group compared to sham and TBI rats. Molecular investigations revealed higher levels of Bax/Bcl2 ratio, Caspase 3, and NF-κB in the TBI+PTZ group compared to the other animal groups. The value of Nrf2 did not change after mild TBI compared to sham and PTZ control groups. Occurrence of seizures after TBI, however, significantly decreased the level of Nrf2. CONCLUSION: Our data indicated that seizure occurrence following mild TBI aggravates cell injury and death via activation of neuroinflammatory processes and may increase the risk of PTE. Additionally, our results suggest a potential protective role of Nrf2 after chemically evoked PTE.

Theta Oscillations Through Hippocampal/Prefrontal Pathway: Importance in Cognitive Performances.

Among various hippocampal rhythms, including sharp-wave ripples, gamma, and theta, theta rhythm is crucial for cognitive processing, particularly learning and memory. Theta oscillations are observable in both humans and rodents during spatial navigations. However, the hippocampus (Hip) is well known as the generator of current rhythm, and other brain areas, such as prefrontal cortex (PFC), can be affected by theta rhythm, too. The PFC is a core structure for the execution of diverse higher cortical functions defined as cognition. This region is connected to the hippocampus through the hippocampal/prefrontal pathway; hereby, theta oscillations convey hippocampal inputs to the PFC and simultaneously synchronize the activity of these two regions during memory, learning and other cognitive tasks. Importantly, thalamic nucleus reunions (nRE) and basolateral amygdala are salient relay structures modulating the synchronization, firing rate, and phase-locking of the hippocampal/prefrontal oscillations. Herein, we summarized experimental studies, chiefly animal researches in which the theta rhythm of the Hip-PFC axis was investigated using either electrophysiological assessments in rodent or integrated diffusion-weighted imaging and electroencephalography in human cases under memory-based tasks. Moreover, we briefly reviewed alterations of theta rhythm in some CNS diseases with the main feature of cognitive disturbance. Interestingly, animal studies implied the interruption of theta synchronization in psychiatric disorders such as schizophrenia and depression. To disclose the precise role of theta rhythm fluctuations through the Hip-PFC axis in cognitive performances, further studies are needed.

Progesterone modulates post-traumatic epileptogenesis through regulation of BDNF-TrkB signaling and cell survival-related pathways in the rat hippocampus.

Female sex hormone, progesterone, in addition to seizure modifying activity is also known as a potential protective agent against various brain injury conditions. Considering the predisposal role of traumatic brain injury (TBI) on developing post-traumatic epilepsy (PTE), the effect of progesterone on post-traumatic epileptogenesis is not investigated yet. Male Wistar rats were given a moderate focal weight drop injury (500 gr) or sham surgery and then progesterone (16 and 32mg/kg) was given daily for two consecutive weeks. On day 15 of injury, seizures were induced by administration of a GABAA receptor antagonist, pentylenetetrazole (PTZ, 30 mg/kg). Seizures were then assessed over a 1-h period using the Racine clinical rating scale. Traumatized animals that received 32 mg/kg progesterone had reduced score, duration of seizures and almost did not show tonic-clonic seizures during 60 min versus the untreated trauma group. In line with behavioral alterations, 32 mg/kg progesterone enhanced the amount of Nrf2 and HO-1 proteins and decreased the level of NF-kB, BDNF, Caspase 3 and ratio of Bax/Bcl-2 in the ipsilateral hippocampus. Additionally, the number of TUNEL-positive apoptotic cells, as well as injured dark neurons in the parietal cortex and hippocampal CA1 of 32 mg/kg-treated animals showed a significant reduction. Administration of 16 mg/kg progesterone elevated production of BDNF, Bax and Caspase 3 and decreased anti-apoptotic Bcl-2 protein. Taken together, an early administration of 32 mg/kg of progesterone after TBI for two weeks post-injury modified seizure activity. Our findings suggest that post-traumatic anti-epileptogenesis property of a high dose of progesterone partly occurs through the manipulation of BDNF-TrkB axis along with control of cell survival pathways.