Hippocampal Abnormalities Research Articles

Human herpesvirus 6 (HHV-6) encephalitis secondary to chimeric antigen receptor (CAR)-T cell therapy.

Human herpesvirus (HHV)-6 encephalitis secondary to chimeric antigen receptor (CAR)-T cell therapyis relatively rare in clinical practice and needs to be differentiated from immune effector cell-associatedneurotoxicity syndrome (ICANS). We retrospectively reported a case of HHV-6 encephalitis secondary to CAR-T cell therapy. A male patient from China with diffuse large B-cell lymphoma underwent chimeric CAR-T cell therapy anddeveloped a generalized rash on the 8th day, followed by cognitive changes, memory loss, and disorientation onthe 14th day after CAR-T cell therapy. Initially, ICANS was suspected. A lumbar puncture was performed on the 18th day. The cerebrospinal fluid (CSF) analysis revealed slightly elevated protein levels and a high presence of HHV-6B sequences by mNGS. Brain MRI showed bilateral hippocampal abnormalities. The patient was ultimatelydiagnosed with HHV-6 encephalitis and treated with ganciclovir and dexamethasone. After one week of treatment,follow-up CSF analysis showed a reduction in HHV-6B sequences. The patient was discharged with improvedmemory and orientation. HHV-6 encephalitis secondary to CAR-T cell therapy may be easily confused with ICANS. Timely andaggressive diagnostic procedures, such as mNGS of CSF and cranial imaging, along with prompt antiviral therapy,are crucial for improving patient outcomes.

Hippocampal microscopic fractional anisotropy is reduced in temporal lobe epilepsy

Abstract Surgical resection is the method of choice for treating drug-resistant focal temporal lobe epilepsy (TLE). Postsurgical outcomes are better when magnetic resonance imaging (MRI) findings can localize the seizure focus for resection. However, many patients are MR-negative, meaning the focus cannot be differentiated from normal tissue in relaxation-weighted MRI. Diffusion MRI shows promise as a preoperative marker of neuronal abnormalities due to its sensitivity to cellular changes such as axon damage, indexed by fractional anisotropy. Microscopic fractional anisotropy is a recently introduced diffusion MRI metric that is sensitive to axon integrity regardless of axon orientation in both grey and white matter. In contrast, regular fractional anisotropy is only sensitive to axon integrity in coherently oriented bundles of fibers. This work investigated whether microscopic fractional anisotropy is sensitive to hippocampal abnormalities in drug-resistant TLE. Diffusion MRI was performed on a 3T scanner in 19 patients (age = 31±10 years) with drug-resistant TLE (of which 10 were MR-negative) and 18 healthy volunteers (age = 38±15). A deep-learning method was employed to segment the hippocampus into smaller subregions corresponding to the subiculum, cornu ammonis (CA) 1, CA2/3, and CA4 plus dentate gyrus (DG). Mean measurements of subregion volume, diffusivity, fractional anisotropy, and microscopic fractional anisotropy were compared between cohorts. In a subset of the TLE cohort suspected to have unilateral pathology (n=15, age = 32±10 years), the percentage differences between measurements ipsilateral and contralateral to the epileptogenic zone were evaluated to assess asymmetry. Microscopic fractional anisotropy was reduced in the hippocampus of drug-resistant TLE patients relative to healthy volunteers. In subregion-specific analysis, microscopic fractional anisotropy was significantly reduced in only the CA4/DG region in patients compared to healthy volunteers, after corrections for multiple comparisons. In the 15 patients with suspected unilateral pathology, microscopic fractional anisotropy was reliably and statistically lower in the ipsilateral CA4/DG region compared to the contralateral side. Significant differences were not observed between TLE patients and healthy volunteers, or between hemispheres for patients with suspected unilateral pathology, for the fractional anisotropy or volume metrics. Diffusion MRI may complement standard imaging procedures by detecting abnormalities in MRI-negative patients. Due to its ability to detect abnormality regardless of axon orientation, microscopic fractional anisotropy may improve seizure focus localization in surgical candidates.

Hippocampal contributions to biologic, behavioral and cognitive deficits in autism: An update review

The most characteristic symptoms for the diagnosis of autism spectrum disorder (ASD) and the future life of the individual are deterioration in social communication and stereotyped or repetitive behaviors. ASD is associated with diverse atypical difficulties, including memory, learning, language, emotion, and cognitive impairment. Consequently, the hippocampus is important for memory, learning, language ability, emotional regulation, and cognitive mapping. Thus, the hippocampus plays an influential role in the pathophysiological mechanisms of ASD. Here, we provide an updated review of hippocampal structural and functional abnormalities and highlight the hippocampus as an important area for future research.

Associations between parental rearing style and amygdala and hippocampal subfield abnormalities in drug-naive females with anorexia nervosa

BackgroundAltered volumes in the hippocampus and amygdala have been linked to anorexia nervosa (AN). This study aimed to investigate amygdala and hippocampal subfields volume abnormalities in AN patients, and their associations with parental rearing practices and clinical psychological characteristics.MethodsThis study included twenty-nine drug-naive females with AN from West China Hospital of Sichuan University, China, and fifty-nine age- and gender-matched healthy controls (HCs) recruited through advertisement. All participants underwent T1-weighted imaging. Amygdala and hippocampal subfields volume was calculated using FreeSurfer 7.0. The Core Self-Evaluation Scale (CSES) and Rosenberg Self-Esteem Scale (RSES) were used to assess the psychological characteristics of AN patients. The Egna Minnen av Barndoms Uppfostran (EMBU) was employed to evaluate parental rearing practices. Group differences in brain volumes were analyzed with covariates like age and total intracranial volume (TIV). Partial correlation analysis explored the correlations between brain region volumes and clinical psychological characteristics.ResultsAN patients exhibited lower RSES and CSES scores, and more adverse parental rearing style than healthy norms. After adjusting for covariates, AN patients showed decreased gray matter volume (GMV) in the left medial (Me) and cortical (Co) nucleus, as well as in the right hippocampal-amygdala transition area (HATA). GMV in the left Me was correlated with years of education among HCs but not among AN patients. GMV in the right HATA was positively correlated with paternal penalty and severity, as well as maternal overinterference.ConclusionThis study supports structure abnormalities in amygdala and hippocampus in AN patients and suggests that parental rearing practices may be associated with hippocampal abnormalities, potentially contributing to the pathophysiology of AN. Addressing appropriate parental rearing styles may offer a positive impact on AN.

Curcumin activates the Wnt/β-catenin signaling pathway to alleviate hippocampal neurogenesis abnormalities caused by intermittent hypoxia: A study based on network pharmacology and experimental verification

The purpose of this work was to investigate how curcumin (Cur) might enhance cognitive function and to gain a better understanding of the molecular mechanisms behind Cur’s impacts on neurogenesis deficits brought on by intermittent hypoxia (IH). Using network pharmacology, we explored possible targets for Cur’s obstructive sleep apnea (OSA) therapy. We established an IH model using C57BL/6 mice and c17.2 cells, and we assessed the influence of Cur on treatment outcomes as well as the effect of IH on cognitive function. Hippocampal damage and neurogenesis, as well as expression of core targets, were then examined. Network pharmacology analysis revealed that Cur has the potential for multi-target, multi-pathway therapy, with CTNNB1 and MYC as core target genes. The Morris water maze test showed that Cur (100 mg/kg, intragastrically) significantly improved cognitive dysfunction induced by IH. The hematoxylin and eosin (H&E) and Nissl staining indicated that Cur could alleviate damage to the hippocampus caused by IH. Immunohistochemistry, immunofluorescence, and western blotting results showed that Cur might promote neurogenesis and upregulate the expression of β-catenin and c-myc. In vitro, Cur (0.5 μM) has a protective effect on IH-induced neural stem cells (NSCs) injury and apoptosis and can restore the Wnt/β-catenin. Cur significantly increased the neurogenesis via the Wnt/β-catenin pathway, providing the scientific groundwork for the development of new treatment strategies for neurological damage linked to OSA.

Validation of a Paralimbic-Related Subcortical Brain Dysmaturation MRI Score in Infants with Congenital Heart Disease.

Background: Brain magnetic resonance imaging (MRI) of infants with congenital heart disease (CHD) shows brain immaturity assessed via a cortical-based semi-quantitative score. Our primary aim was to develop an infant paralimbic-related subcortical-based semi-quantitative dysmaturation score, termed brain dysplasia score (BDS), to detect abnormalities in CHD infants compared to healthy controls and secondarily to predict clinical outcomes. We also validated our BDS in a preclinical mouse model of hypoplastic left heart syndrome. Methods: A paralimbic-related subcortical BDS, derived from structural MRIs of infants with CHD, was compared to healthy controls and correlated with clinical risk factors, regional cerebral volumes, feeding, and 18-month neurodevelopmental outcomes. The BDS was validated in a known CHD mouse model named Ohia with two disease-causing genes, Sap130 and Pchda9. To relate clinical findings, RNA-Seq was completed on Ohia animals. Findings: BDS showed high incidence of paralimbic-related subcortical abnormalities (including olfactory, cerebellar, and hippocampal abnormalities) in CHD infants (n = 215) compared to healthy controls (n = 92). BDS correlated with reduced cortical maturation, developmental delay, poor language and feeding outcomes, and increased length of stay. Ohia animals (n = 63) showed similar BDS findings, and RNA-Seq analysis showed altered neurodevelopmental and feeding pathways. Sap130 mutants correlated with a more severe BDS, whereas Pcdha9 correlated with a milder phenotype. Conclusions: Our BDS is sensitive to dysmaturational differences between CHD and healthy controls and predictive of poor outcomes. A similar spectrum of paralimbic and subcortical abnormalities exists between human and Ohia mutants, suggesting a common genetic mechanistic etiology.

Network Pharmacology and Validation of the Combinative Therapy of Ligusticum striatum DC. and Borneolum against Cerebral Ischemia

Background: Ligusticum striatum DC. (LDC) is often prescribed for Cerebral Ischemia (CI) and is commonly combined with Borneolum (BO) to enhance therapeutic outcomes. However, its specific active ingredients and underlying mechanisms remain unclear. Objective: This study aimed to identify the active ingredients and mechanisms of LDC and BO combination therapy against CI using network pharmacology, molecular docking, and in vivo experiments. Methods: Potential active ingredients and targets were sourced from relevant databases, and a drug-component-target-disease network was constructed to pinpoint key ingredients. Subsequently, a protein-protein interaction analysis was conducted to confirm the key targets. Following enrichment analyses of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), molecular docking was employed to evaluate binding energies. Finally, the therapeutic effects and mechanisms of the combination against CI were validated through in vivo experiments using male ICR mice Results: Venn analysis identified a total of 41 components and 292 potential targets. The drugcomponent-target-disease network revealed that the key components in LDC were palmitic acid, tetramethylpyrazine, and (Z)-ligustilide, while those in BO were (+)-borneol, β-elemene, and (-)- borneol. The PPI analysis highlighted seven crucial targets. Docking results confirmed a stable affinity between these components and their targets. KEGG enrichment analysis indicated that the mechanism involved the PI3K/AKT signaling pathway. Subsequently, in vivo experiments confirmed that the combination ameliorated abnormal hippocampus morphology and reduced the release of inflammatory factors through the activation of the PI3K/AKT signaling pathway Conclusion: The combination of LDC and BO markedly improved CI and inhibited inflammation response via activating the PI3K/AKT pathway

The Hippocampus: Anatomy, Function and Clinical Correlation

The hippocampus is a brain region situated deep within the temporal lobe. The hippocampus houses the archipallium cortex, which includes components such as the dentate gyrus, cornu ammonis, and subiculum. Each structure contains different layers and relates to structures around the hippocampus through afferent and efferent nerves.The coupling of afferent and efferent fibers is crucial in supporting the hippocampal function related to memory formation, learning, spatial navigation, and emotion regulation. Previous studies have shown that several neurological diseases are associated with hippocampus abnormalities. The transformations in the hippocampus, spanning from molecular to morphological alterations, have been extensively researched. Progress in science and technology has facilitated a more detailed examination of the hippocampus structure.This article will explore the typical anatomical configuration of the hippocampus, its functionality, and its connections with neighboring structures. Furthermore, it will also address hippocampus alterations in various disease states.

Antiphospholipid Antibodies in Mental Disorders.

Thrombotic events striking the central nervous system are clinical criteria for the antiphospholipid syndrome (APS). Besides these, neuropsychiatric non-APS criteria manifestations are increasingly described in patients with persistently positive antiphospholipid antibodies (aPL). Among these are psychiatric manifestations. Animal models mainly describe hyperactive behavior and anxiety associated with hippocampal abnormalities. Cases of associations with psychosis, mood disorders, bipolarity, anxiety, obsessive-compulsive behavior, and depression have been reported but are still rare. Systematic human clinical association studies are concordant with a risk of psychosis, depression (simple to major), and anxiety disorders, but these are limited and of inconstant methodological quality. Brain imaging in patients, also insufficiently investigated, shows early signs of hypoperfusion and of subtle diffuse white matter changes compatible with an alteration of the axonal structure and changes in the myelin sheath. Direct interactions of aPL with the brain cells, both on cell lines and on animal and human brain biopsies, targeting both glial cells, astrocytes, and neurons, can be demonstrated. These clusters of arguments make the association between psychiatric diseases and aPL increasingly plausible. However, a considerable amount of clinical research must still be performed in accordance with the highest standards of methodological quality. The therapeutic management of this association, in terms of both prevention and cure, currently remains unresolved.

Hippocampus diffusivity abnormalities in classical trigeminal neuralgia

Abstract Introduction: Patients with chronic pain frequently report cognitive symptoms that affect memory and attention, which are functions attributed to the hippocampus. Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder characterized by paroxysmal attacks of unilateral orofacial pain. Given the stereotypical nature of TN pain and lack of negative symptoms including sensory loss, TN provides a unique model to investigate the hippocampal implications of chronic pain. Recent evidence demonstrated that TN is associated with macrostructural hippocampal abnormalities indicated by reduced subfield volumes; however, there is a paucity in our understanding of hippocampal microstructural abnormalities associated with TN. Objectives: To explore diffusivity metrics within the hippocampus, along with its functional and structural subfields, in patients with TN. Methods: To examine hippocampal microstructure, we utilized diffusion tensor imaging in 31 patients with TN and 21 controls. T1-weighted magnetic resonance images were segmented into hippocampal subfields and registered into diffusion-weighted imaging space. Fractional anisotropy (FA) and mean diffusivity were extracted for hippocampal subfields and longitudinal axis segmentations. Results: Patients with TN demonstrated reduced FA in bilateral whole hippocampi and hippocampal body and contralateral subregions CA2/3 and CA4, indicating microstructural hippocampal abnormalities. Notably, patients with TN showed significant correlation between age and hippocampal FA, while controls did not exhibit this correlation. These effects were driven chiefly by female patients with TN. Conclusion: This study demonstrates that TN is associated with microstructural hippocampal abnormalities, which may precede and potentially be temporally linked to volumetric hippocampal alterations demonstrated previously. These findings provide further evidence for the role of the hippocampus in chronic pain and suggest the potential for targeted interventions to mitigate cognitive symptoms in patients with chronic pain.

Nicotinamide riboside alleviates brain dysfunction induced by chronic cerebral hypoperfusion via protecting mitochondria

Chronic cerebral hypoperfusion (CCH) is an enduring inadequate blood flow to the brain, resulting in vascular dementia (VaD). However, the effective treatment strategies are lacking. Supplementing with nicotinamide adenine dinucleotide (NAD+) has shown neuroprotective benefits in other neurodegenerative disorders. Nicotinamide riboside (NR), as a precursor of NAD+, is believed to hold promise in improving mitochondrial health, autophagy, and cognitive function. Meanwhile, NR has unique oral bioavailability, good tolerability, and minimal side effects, and it is the most promising for clinical translation. However, the effectiveness of NR in treating CCH-related VaD is still uncertain. The present study examined the neuroprotective effects of NR supplementation and its underlying mechanisms in a CCH rat model. The rats with CCH were given NR at a daily dosage of 400 mg/kg for 3 months. NR supplementation increased blood and brain NAD+ levels and improved brain function in CCH rats, including cognitive function and oxygenation capacity. It also reduced hippocampal neuronal loss and abnormalities and mitigated the decrease in dendritic spine density. The analysis of RNA sequencing in hippocampal tissue supports these findings. Electron microscopy and protein detection results suggest that NR may maintain mitochondrial structural integrity and exert a protective role by attenuating mitochondrial fission and impaired autophagy flux caused by CCH. In conclusion, these findings offer evidence for the neuroprotective potential of NR supplementation in ameliorating cognitive impairment induced by CCH.

Insights into the structure and function of the hippocampus: implications for the pathophysiology and treatment of autism spectrum disorder.

The hippocampus is one of the brain areas affected by autism spectrum disorder (ASD). Individuals with ASD typically have impairments in hippocampus-dependent learning, memory, language ability, emotional regulation, and cognitive map creation. However, the pathological changes in the hippocampus that result in these cognitive deficits in ASD are not yet fully understood. In the present review, we will first summarize the hippocampal involvement in individuals with ASD. We will then provide an overview of hippocampal structural and functional abnormalities in genetic, environment-induced, and idiopathic animal models of ASD. Finally, we will discuss some pharmacological and non-pharmacological interventions that show positive impacts on the structure and function of the hippocampus in animal models of ASD. A further comprehension of hippocampal aberrations in ASD might elucidate their influence on the manifestation of this developmental disorder and provide clues for forthcoming diagnostic and therapeutic innovation.

GSDMD/Drp1 signaling pathway mediates hippocampal synaptic damage and neural oscillation abnormalities in a mouse model of sepsis-associated encephalopathy.

Gasdermin D (GSDMD)-mediated pyroptotic cell death is implicated in the pathogenesis of cognitive deficits in sepsis-associated encephalopathy (SAE), yet the underlying mechanisms remain largely unclear. Dynamin-related protein 1 (Drp1) facilitates mitochondrial fission and ensures quality control to maintain cellular homeostasis during infection. This study aimed to investigate the potential role of the GSDMD/Drp1 signaling pathway in cognitive impairments in a mouse model of SAE. C57BL/6 male mice were subjected to cecal ligation and puncture (CLP) to establish an animal model of SAE. In the interventional study, mice were treated with the GSDMD inhibitor necrosulfonamide (NSA) or the Drp1 inhibitor mitochondrial division inhibitor-1 (Mdivi-1). Surviving mice underwent behavioral tests, and hippocampal tissues were harvested for histological analysis and biochemical assays at corresponding time points. Haematoxylin-eosin staining and TUNEL assays were used to evaluate neuronal damage. Golgi staining was used to detect synaptic dendritic spine density. Additionally, transmission electron microscopy was performed to assess mitochondrial and synaptic morphology in the hippocampus. Local field potential recordings were conducted to detect network oscillations in the hippocampus. CLP induced the activation of GSDMD, an upregulation of Drp1, leading to associated mitochondrial impairment, neuroinflammation, as well as neuronal and synaptic damage. Consequently, these effects resulted in a reduction in neural oscillations in the hippocampus and significant learning and memory deficits in the mice. Notably, treatment with NSA or Mdivi-1 effectively prevented these GSDMD-mediated abnormalities. Our data indicate that the GSDMD/Drp1 signaling pathway is involved in cognitive deficits in a mouse model of SAE. Inhibiting GSDMD or Drp1 emerges as a potential therapeutic strategy to alleviate the observed synaptic damages and network oscillations abnormalities in the hippocampus of SAE mice.

Revealing complexity: beyond the whole—segmentation of hippocampal subfields in adolescents with depression and its relationships with cognition

IntroductionThe occurrence of depression in adolescence, a critical period of brain development, linked with neuroanatomical and cognitive abnormalities. Neuroimaging studies have identified hippocampal abnormalities in those of adolescent patients. However, few studies have investigated the atypically developmental trends in hippocampal subfields in adolescents with depression and their relationships with cognitive dysfunctions.ObjectivesTo explore the structural abnormalities of hippocampal subfields in patients with youth depression and examine how these abnormalities associated with cognitive deficits.MethodsWe included a sample of 79 first-episode depressive patients (17 males, age = 15.54±1.83) and 71 healthy controls (23 males, age = 16.18±2.85). The severity of these adolescent patients was assessed by depression scale, suicidal risk and self-harm behavior. Nine cognitive tasks were used to evaluate memory, cognitive control and attention abilities for all participants. Bilateral hippocampus were segmented into 12 subfields with T1 and T2 weighted images using Freesurfer v6.0. A mixed analysis of variance was performed to assess the differences in subfields volumes between all patients and controls, and between patients with mild and severe depression. Finally, LASSO regression was conducted to explore the associations between hippocampal subfields and cognitive abnormalities in patients.ResultsWe found significant subfields atrophy in the CA1, CA2/3, CA4, dentate gyrus, hippocampal fissure, hippocampal tail and molecular layer subfields in patients. For those patients with severe depression, hippocampal subfields showed greater extensive atrophy than those in mild, particularly in CA1-4 subfields extending towards the subiculum. These results were similar across various severity assessments. Regression indicated that hippocampal subfields abnormalities had the strongest associations with memory dysfunction, and relatively week associations with cognitive control and attention. Notably, CA4 and dentate gyrus had the highest weights in the regression model.ConclusionsAs depressive severity increases, hippocampal subfield atrophy tends to spread from CA regions to surrounding areas, and primarily affects memory function in patients with youth depression. These results suggest hippocampus might be markers in progression of adolescent depression, offering new directions for early clinical intervention.Disclosure of InterestNone Declared

Hippocampal Abnormalities as a Biological Mechanism in Chronic Pain: A Critical Review

Chronic pain is a common medical issue that impacts the daily lives of more than 50 million Americans making it the leading cause of disability in the United States and the most common reason people seek medical care. Studies have shown that the limbic system plays an important part in the experience of chronic pain, however, of all the components of the corticolimbic system, the hippocampus has been studied less systematically in terms of its impact on chronic pain. This paper analyzed four studies that were published between 2019 and 2023 that examined the role of hippocampal abnormalities in chronic pain patients to provide a critical review of the emerging literature on this topic. The focus of the papers included in this critical review encompasses a variety of chronic pain disorders and sources of pain. For each study, an overview of the methodology, main findings, and limitations was provided.

Longitudinal hippocampal subfield development associated with psychotic experiences in young people

Hippocampal volumetric reductions are observed across the psychosis spectrum, with interest in the localisation of these reductions within the hippocampal subfields increasing. Deficits of the CA1 subfield in particular have been implicated in the neuropathophysiology of psychotic disorders. Investigating the trajectory of these abnormalities in healthy adolescents reporting sub-threshold psychotic experiences (PE) can provide insight into the neural mechanisms underlying psychotic symptoms without the potentially confounding effects of a formal disorder, or antipsychotic medication. In this novel investigation, a sample of 211 young people aged 11-13 participated initially in the Adolescent Brain Development study. PE classification was determined by expert consensus at each timepoint. Participants underwent neuroimaging at 3 timepoints, over 6 years. 78 participants with at least one scan were included in the final sample; 33 who met criteria for a definite PE at least once across all the timepoints (PE group), and 45 controls. Data from bilateral subfields of interest (CA1, CA2/3, CA4/DG, presubiculum and subiculum) were extracted for Linear Mixed Effects analyses. Before correction, subfield volumes were found to increase in the control group and decrease in the PE group for the right CA2 and CA2/3 subfields, with moderate to large effect sizes (d = −0.61, and d = −0.79, respectively). Before correction, right subiculum and left presubiculum volumes were reduced in the PE group compared to controls, regardless of time, with moderate effect sizes (d = −0.52, and d = −0.59, respectively). However, none of these effects survived correction. Severity of symptoms were not associated with any of the noted subfields. These findings provide novel insight to the discussion of the role of hippocampal subfield abnormalities in the pathophysiology underlying psychotic experiences.

Rehmanniae Radix Preparata ameliorates behavioral deficits and hippocampal neurodevelopmental abnormalities in ADHD rat model.

Abnormal hippocampal neurodevelopment, particularly in the dentate gyrus region, may be a key mechanism of attention-deficit/hyperactivity disorder (ADHD). In this study, we investigate the effect of the most commonly used Chinese herb for the treatment of ADHD, Rehmanniae Radix Preparata (RRP), on behavior and hippocampal neurodevelopment in spontaneously hypertensive rats (SHR). Behavior tests, including Morris water maze (MWM) test, open field test (OFT) and elevated plus maze (EPM) test were performed to assess the effect of RRP on hyperactive and impulsive behavior. Hippocampal neurodevelopment was characterized by transmission electron microscopy, immunofluorescence, Golgi staining and Nissl staining approaches. Regulatory proteins such as Trkb, CDK5, FGF2/FGFR1 were examined by Western blot analysis. The results showed that RRP could effectively control the impulsive and spontaneous behavior and improve the spatial learning and memory ability. RRP significantly reduced neuronal loss and increased the number of hippocampal stem cells, and promoted synaptic plasticity. In addition, FGF/FGFR signaling was upregulated after RRP treatment. RRP can effectively reduce impulsive and spontaneous behavior and ameliorate hippocampal neurodevelopmental abnormalities in ADHD rat model.

Improving Diagnostic Performance of MRI for Temporal Lobe Epilepsy With Deep Learning-Based Image Reconstruction in Patients With Suspected Focal Epilepsy.

To evaluate the diagnostic performance and image quality of 1.5-mm slice thickness MRI with deep learning-based image reconstruction (1.5-mm MRI + DLR) compared to routine 3-mm slice thickness MRI (routine MRI) and 1.5-mm slice thickness MRI without DLR (1.5-mm MRI without DLR) for evaluating temporal lobe epilepsy (TLE). This retrospective study included 117 MR image sets comprising 1.5-mm MRI + DLR, 1.5-mm MRI without DLR, and routine MRI from 117 consecutive patients (mean age, 41 years; 61 female; 34 patients with TLE and 83 without TLE). Two neuroradiologists evaluated the presence of hippocampal or temporal lobe lesions, volume loss, signal abnormalities, loss of internal structure of the hippocampus, and lesion conspicuity in the temporal lobe. Reference standards for TLE were independently constructed by neurologists using clinical and radiological findings. Subjective image quality, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were analyzed. Performance in diagnosing TLE, lesion findings, and image quality were compared among the three protocols. The pooled sensitivity of 1.5-mm MRI + DLR (91.2%) for diagnosing TLE was higher than that of routine MRI (72.1%, P < 0.001). In the subgroup analysis, 1.5-mm MRI + DLR showed higher sensitivity for hippocampal lesions than routine MRI (92.7% vs. 75.0%, P = 0.001), with improved depiction of hippocampal T2 high signal intensity change (P = 0.016) and loss of internal structure (P < 0.001). However, the pooled specificity of 1.5-mm MRI + DLR (76.5%) was lower than that of routine MRI (89.2%, P = 0.004). Compared with 1.5-mm MRI without DLR, 1.5-mm MRI + DLR resulted in significantly improved pooled accuracy (91.2% vs. 73.1%, P = 0.010), image quality, SNR, and CNR (all, P < 0.001). The use of 1.5-mm MRI + DLR enhanced the performance of MRI in diagnosing TLE, particularly in hippocampal evaluation, because of improved depiction of hippocampal abnormalities and enhanced image quality.

Increased A1 astrocyte activation-driven hippocampal neural network abnormality mediates delirium-like behavior in aged mice undergoing cardiac surgery.

Delirium is the most common neurological complication after cardiac surgery with adverse impacts on surgical outcomes. Advanced age is an independent risk factor for delirium occurrence but its underlying mechanisms are not fully understood. Although increased A1 astrocytes and abnormal hippocampal networks are involved in neurodegenerative diseases, whether A1 astrocytes and hippocampal network changes are involved in the delirium-like behavior of aged mice remains unknown. In the present study, a mice model of myocardial ischemia-reperfusion mimicking cardiac surgery and various assessments were used to investigate the different susceptibility of the occurrence of delirium-like behavior between young and aged mice and the underlying mechanisms. The results showed that surgery significantly increased hippocampal A1 astrocyte activation in aged compared to young mice. The high neuroinflammatory state induced by surgery resulted in glutamate accumulation in the extrasynaptic space, which subsequently decreased the excitability of pyramidal neurons and increased the PV interneurons inhibition through enhancing N-methyl-D-aspartate receptors' tonic currents in the hippocampus. These further induced the abnormal activities of the hippocampal neural networks and consequently contributed to delirium-like behavior in aged mice. Notably, the intraperitoneal administration of exendin-4, a glucagon-like peptide-1 receptor agonist, downregulated A1 astrocyte activation and alleviated delirium-like behavior in aged mice, while IL-1α, TNF-α, and C1q in combination administered intracerebroventricularly upregulated A1 astrocyte activation and induced delirium-like behavior in young mice. Therefore, our study suggested that cardiac surgery increased A1 astrocyte activation which subsequently impaired the hippocampal neural networks and triggered delirium development.

Abnormalities of hippocampal shape in idiopathic normal‐pressure hydrocephalus patients

AbstractBackgroundWe utilized 3‐dimensional, surface‐based, morphometric analysis to investigate hippocampus shape between 2 groups: (1) idiopathic normal‐pressure hydrocephalus (INPH) patients who had a positive response to the cerebrospinal fluid tap test and (2) healthy controls. The aims were (1) to evaluate INPH‐related structural abnormalities of the hippocampi and (2) to investigate relationships between hippocampal shape changes and gait disturbance in INPH patients.MethodForty‐eight INPH patients and 25 healthy controls were imaged with MRI, including 3‐dimensional volumetric images, for vertex‐based 3‐dimensional hippocampal shape analysis.ResultVertex‐wise shape analysis revealed significant bilateral deformation in patients with INPH compared with healthy controls after FDR correction. Both the left and right hippocampi were more elongated and narrowed in INPH patients than in the healthy controls. In both hemispheres, INPH patients demonstrated an upward bending of the middle and posterior hippocampus reflecting a bilateral vertical displacement from body to tail. Significant correlations were found between local shape deformity and the timed up and go and 10 meter walking tests (to a greater degree on the right than on the left). Bilateral inward deformations at the superomedial hippocampal tail and inferior hippocampal body were consistently associated with inferior performance across tests. Inward deformations at the right medial and lateral hippocampal head and right superior hippocampal body were also consistently associated with worse performance across tests.ConclusionThese results suggest that patients with INPH have unique patterns of hippocampal shape changes. Our findings encourage future studies to elucidate the underlying mechanism of hippocampal morphometric abnormalities in INPH patients. Changes in overall shape may contribute to the distinctive gait abnormalities associated with INPH.