Normal Hippocampus Research Articles

Dose-Painting Proton Radiotherapy Guided by Functional MRI in Non-enhancing High-Grade Gliomas

AimsThis study aimed to demonstrate the feasibility and evaluate the dosimetric effect and clinical impact of dose-painting proton radiotherapy (PRT) guided by functional MRI in non-enhancing high-grade gliomas (NE-HGGs). Materials and methodsThe 3D-ASL and T2 FLAIR MR images of ten patients with NE-HGGs before radiotherapy were studied retrospectively. The hyperintensity on T2 FLAIR was used to generate the planning target volume (PTV), and the high-perfusion volume on 3D-ASL (PTV-ASL) was used to generate the simultaneous integrated boost (SIB) volume. Each patient received pencil beam scanning PRT and photon intensity-modulated radiotherapy (IMRT). There were five plans in each modality: (1) Uniform plans (IMRT60 vs. PRT60): 60Gy in 30 fractions to the PTV. (2)–(5) SIB plans (IMRT72, 84, 96, 108 vs. PRT72, 84, 96, 108): Uniform plan plus additional dose boost to PTV-ASL in 30 fractions to 72, 84, 96, 108 Gy. The dosimetric differences between various plans were compared. The clinical effects of target volume and organs at risk (OARs) were assessed using biological models for both tumor control probability (TCP) and normal tissue complication probability (NTCP). ResultsCompared with the IMRT plan, the D2 and D50 of the PRT plans with the same prescription dose increased by 1.27–4.12% and 0.64–2.01%, respectively; the R30 decreased by > 32%; the dose of brainstem and chiasma decreased by > 27% and >32%; and the dose of normal brain tissue (Br-PTV), optic nerves, eyeballs, lens, cochlea, spinal cord, and hippocampus decreased by > 50% (P < 0.05). The maximum necessary dose was 96GyE to achieve >98% TCP for PRT, and it was 84Gy to achieve >91% TCP for IMRT. The average NTCP of Br-PTV was 1.30% and 1.90% for PRT and IMRT at the maximum dose escalation, respectively. The NTCP values of the remaining OARs approached zero in all PRT plans. ConclusionThe functional MRI-guided dose escalation using PRT is feasible while sparing the OARs constraints and demonstrates a potential clinical benefit by improving TCP with no or minimal increase in NCTP for tissues outside the PTV. This retrospective study suggested that the use of PRT-based SIB guided by functional MRI may represent a strategy to provide benefits for patients with NE-HGGs.

Evaluation of Effect of Piroxicam on the Hippocampus of Adult Sprague-Dawley Rats

Background: Studies have shown that some non-steroidal anti-inflammatory drugs (NSAIDs) can affect the hippocampus, a brain region crucial for memory and learning. Piroxicam is a widely used NSAID for providing relief from menstrual pain and associated symptoms in women with dysmenorrhea. Its potential effect on the hippocampus requires investigation. Objective: The objective was to determine the potential neurotoxic effect of piroxicam on the hippocampus of female rats using the Sprague –Dawley rats as models. Materials and Methods: A total of twenty adult female Wistar rats weighing 110g ± 20g (n=20, A-D) were used. Group A was control, B-D received 10, 20 and 40mg/kg of Piroxicam orally respectively for 2 weeks. After this study, the rats were euthanised and their brain was harvested for histological observations. Blood samples were also taken for the analysis of the oxidative stress markers i.e. Superoxide Dismutase (SOD), Catalase (CAT) and Malondialdehyde (MDA). Results: The photomicrographs of the hippocampus of Group A-D showed normal hippocampus with normal neuronal cells, the structural organisation of the CA1- CA4 (sub-regions of the hippocampus) also appeared normal and the dentate gyrus appeared normal. There was significant increase in MDA values in the hippocampus of piroxicam-treated rats compared to the control group (p &lt; 0.05) and no significant decrease in SOD and CAT values. Conclusion: The study showed that piroxicam did not damage the structure of the hippocampus despite the induction of oxidative stress in the rats. These findings suggest a potential neuroprotective role for piroxicam in memory impairment scenarios

Effect of Sevoflurane Anesthesia on Intraoperative Spikes, High-Frequency Oscillations, and Phase-Amplitude Coupling in MRI-Normal Hippocampus.

The purpose of this study was to determine the effect of sevoflurane anesthesia on spikes, high-frequency oscillations (HFOs), and phase-amplitude coupling using a modulation index in MRI-normal hippocampus, with the aim of evaluating the utility of intraoperative electrocorticography in identifying the epileptogenic hippocampus during sevoflurane administration. Eleven patients with intractable temporal lobe epilepsy with a normal hippocampus on MRI underwent extra-operative electrocorticography evaluation. Patients were assigned to the Ictal (+) or Ictal (-) group depending on whether the parahippocampal gyrus was included in the seizure onset zone. Intraoperative electrocorticography was performed under 0.5 and 1.5 minimum alveolar concentration of sevoflurane. The rates of spikes, ripples, fast ripples (FRs), ripples on spikes, FRs on spikes, and MI HFO(3-4 Hz) were evaluated. During the intraoperative electrocorticography procedure, sevoflurane administration was found to significantly increase the rate of spikes, ripples on spikes, fast ripples on spikes, and MI HFO(3-4 Hz) in the Ictal (+) group (P < 0.01). By contrast, the Ictal (-) group exhibited a paradoxical increase in the rate of ripples and fast ripple (P < 0.05). Our findings indicate that the administration of sevoflurane during intraoperative electrocorticography in patients with MRI-normal hippocampus can lead to a dose-dependent enhancement of epileptic biomarkers (spikes, ripples on spikes, fast ripples on spikes, and MI (HFO 3-4)) in the epileptogenic hippocampus, while paradoxically increasing the rate of ripples and fast ripple in the nonepileptogenic hippocampus. These results have significant implications for the identification of the MRI-normal hippocampus that requires surgical intervention and preservation of the nonepileptogenic hippocampus.

Saffron carotenoids reversed the UCMS-induced depression and anxiety in rats: Behavioral and biochemical parameters, and hippocampal BDNF/ERK/CREB and NR2B signaling markers

BackgroundDepression is a debilitating condition that affects the mind and the individual's body. The improving effects of saffron on depression and anxiety have long been discussed, with limited information about the molecular mechanism of action. Hypothesis/PurposeInvestigating the effect of saffron carotenoids, Crocin and Crocetin, on depression and anxiety in rats by emphasizing some signaling pathways involved. Study DesignDepression and anxiety were induced in rats via unpredictable chronic mild stress (UCMS). Then different rat groups were treated with Crocin, Crocetin, Fluoxetine, and vehicle. Behavioral tests were done before and after treatment. MethodsThe serum Serotonin and Corticosterone and the expression of some hippocampal signaling proteins were studied. Furthermore, bioinformatics tools were used to predict the interactions of Crocin/ Crocetin with the Serotonin transporter and NMDA receptor subunit NR2B. Then, the patch-clamp was used to study the interaction of Crocetin with the NMDA receptor. ResultsVarious behavioral tests confirmed the induction of depression and the improvement of depression by these natural carotenoids. In addition, Crocin/ Crocetin significantly increased the decreased serum Serotonin and reduced the increased serum Corticosterone in the depressed groups. They also increased or caused a trend of increase in the CREB, ERK, BAD, BDNF, p11, and 5-HT1B expression in the hippocampus of the depressed groups. In addition, there were an increase or a trend in p-CREB/CREB, p-ERK1/2 /ERK1/2, and p-BAD/BAD ratios in the Crocin/ Crocetin treated depressed groups. However, the NR2B and FOXO3a expression showed a trend of decrease in depressed groups after treatment. The bioinformatics data indicated that Crocin/ Crocetin could bind to the Serotonin transporter (SLC6A4) and NR2B subunit of the NMDA receptor. Both carotenoids bind to the same site as Fluoxetine in the SLC6A4. However, they bound to different sites on the NR2B. So, Crocetin binds to NR2B at the same site as Ifenprodil. But Crocin bound to another site. The whole cell patch-clamp recording on the normal rat hippocampus revealed a significant decrease in the NMDA peak amplitude after Crocetin treatment, indicating its inhibitory effect on this receptor. ConclusionThe antidepressant activities of Crocin/ Crocetin are possibly due to their effects on Serotonin and Corticosterone serum concentrations, NR2B expression, and the downstream signaling pathways. Furthermore, these natural carotenoids, like Fluoxetine, induced an increasing tendency in p11 and 5HT1B in depressed rats.

Left Temporal Pole Encephalocele With Independent Hippocampal Seizures: Surgical Strategy and Relevance of Epileptic Biomarkers.

Temporal pole encephalocele (TE) is an increasingly recognized surgically treatable subtype of refractory temporal lobe epilepsy that rarely shows hippocampal involvement. A 27-year-old patient presented with medically intractable epilepsy because of a left temporal pole encephalocele with a normal hippocampus on MRI. Extraoperative electrocorticography showed independent seizure onset with distinct morphology of seizure onset pattern from the temporal pole encephalocele and hippocampus. Additional analysis of ictal and interictal fast ripples revealed different electrophysiological fast ripple profiles in the two seizure onset zones. The patient underwent temporopolar disconnection, eliminating the need for large dural repair and multiple hippocampal transections that helped preserve the intrahippocampal and extrahippocampal memory pathways. Herein, the authors report that independent hippocampal seizures can be observed in patients with temporal pole encephalocele. Features of the ictal and interictal fast ripples can differ depending on the morphology of the seizure onset pattern. The authors suggest that, the interpretation of fast ripples in clinical practice should take seizure onset patterns into consideration.

Inhibition of NLRP3 alleviated chemotherapy-induced cognitive impairment in rats

Chemotherapy results in long-term effects on cognitive dysfunction called chemotherapy-induced cognitive impairment (CICI) in cancer survivors. However, little is known about the potential molecular mechanisms of CICI. This study aimed to determine the role and potential underlying mechanisms of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome in cognitive impairments induced by chemotherapeutic agents commonly used in breast cancer. The cognitive effects of chemotherapy were investigated in a rat model using the cocktail of doxorubicin and cyclophosphamide. The NLRP3 pathway was found to be differentially expressed after chemotherapy by iTRAQ-based proteomic analysis of normal and chemotherapeutic hippocampi. Treatment with the NLRP3 inhibitor MCC950 following chemotherapy significantly reduced cognitive impairment and decreased the expression of NLRP3, caspase-1 and ASC. Chemotherapy led to increased expression of the glial response markers Iba-1 and GFAP and the axonal injury markers NF-L and NF-M, an elevated number of apoptotic cells and enhanced microstructural damage to axons and mitochondria, while MCC950 treatment alleviated the glial response, cell death and axonal injury. The protective effect of MCC950 was related to the NLRP3 pathway and levels of inflammatory cytokines (TNF-α, IL-1β, IL-18, IL-6, IL-4, and IL-10) and oxidative stress-responsive markers (SOD, MDA, CAT and GSH). The results indicate that CICI is associated with NLRP3 pathway-induced oxidative damage and the inflammatory response and provide a potential therapeutic target to treat cognitive impairment after chemotherapy (doxorubicin and cyclophosphamide)

Neuroprotective Effect of miR-483-5p Against Cardiac Arrest-Induced Mitochondrial Dysfunction Mediated Through the TNFSF8/AMPK/JNK Signaling Pathway

Substantial morbidity and mortality are associated with postcardiac arrest brain injury (PCABI). MicroRNAs(miRNAs) are essential regulators of neuronal metabolism processes and have been shown to contribute to alleviated neurological injury after cardiac arrest. In this study, we identified miRNAs related to the prognosis of patients with neurological dysfunction after cardiopulmonary resuscitation based on data obtained from the Gene Expression Omnibus (GEO) database. Then, we explored the effects of miR-483-5p on mitochondrial biogenesis, mitochondrial-dependent apoptosis, and oxidative stress levels after ischemia‒reperfusion injury in vitro and in vivo. MiR-483-5p was downregulated in PC12 cells and hippocampal samples compared with that in normal group cells and hippocampi. Overexpression of miR-483-5p increased the viability of PC12 cells after ischemia‒reperfusion injury and reduced the proportion of dead cells. A western blot analysis showed that miR-483-5p increased the protein expression of PCG-1, NRF1, and TFAM and reduced the protein expression of Bax and cleaved caspase 3, inhibiting the release of cytochrome c from mitochondria and alleviating oxidative stress injury by inhibiting the production of ROS and reducing MDA activity. We confirmed that miR-483-5p targeted TNFSF8 to regulate the AMPK/JNK pathway, thereby playing a neuroprotective role after cardiopulmonary resuscitation. Hence, this study provides further insights into strategies for inhibiting neurological impairment after cardiopulmonary resuscitation and suggests a potential therapeutic target for PCABI.

Is Hippocampal Resection Necessary for Low-Grade Epilepsy-Associated Tumors in the Temporal Lobe?

Low-grade epilepsy-associated tumors (LEATs) are common in the temporal lobe and can cause drug-resistant epilepsy. Complete resection of LEATs is sufficient for seizure relief. However, hippocampal resection might result in postoperative cognitive impairment. This study aimed to clarify the necessity of hippocampal resection for seizure and cognitive outcomes in patients with temporal lobe LEATs and a normal hippocampus. The study included 32 patients with temporal lobe LEATs and without hippocampal abnormalities. All patients underwent gross total resection as treatment for drug-resistant epilepsy at our tertiary epilepsy center from 2005 to 2020, followed by at least a 12-month follow-up period. Seizure and cognitive outcomes were compared between patients who underwent additional hippocampal resection (Resected group) and those who did not (Preserved group). Among the participants, 14 underwent additional hippocampal resection and 28 (87.5%) achieved seizure freedom irrespective of hippocampal resection. The seizure-free periods were not different between the two groups. Additional hippocampal resection resulted in a significantly negative impact on the postoperative verbal index. In conclusion, additional hippocampal resection in patients with temporal lobe LEATs without hippocampal abnormalities is unnecessary because lesionectomy alone results in good seizure control. Additional hippocampal resection may instead adversely affect the postoperative language function.

KS01.5.A Impact of reduced treatment volumes on pattern of tumor recurrence and radiation dose to normal brain parenchyma in glioblastoma

Abstract Background to analyze GBM recurrence pattern after standard chemoradiotherapy according to different target volume delineations. We hypothesized that reduced target volume margins may result in similar pattern of failure. Material and Methods 207 patients with GBM who recurred after standard chemoradiation were evaluated. According to the Advisory Committee for Radiation Oncology Practice (ACROP) committee of the European Organisation for Research and Treatment of Cancer (EORTC) target volume delineation guideline, the clinical target volume (CTV) used for treatment planning consisted of residual tumor and resection cavity plus 2-cm margin. MRI scans showing tumor recurrences were fused with the planning computed tomography (CT), and the patterns of failure were analyzed dosimetrically using dose-volume histograms. The recurrent lesions were defined as in-field, marginal, or distant if &amp;gt;80%, 20-80%, or &amp;lt;20% of the intersecting volume was included in the 95% isodose line. For each patient a theoretical plan consisting of a reduced CTV using 1-cm margin was created and patterns of failure evaluated. Results The median overall survival and progression-free survival were 15.3 months and 7.8 months, respectively, from the date of surgery. Recurrences were in-field in 180 patients, marginal in 5 patients, and distant in 22 patients. Analysis of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status showed different recurrence patterns of GBMs in patients with MGMT methylated compared with patients with MGMT unmethylated status. Recurrences occurred in-field and distant in 75.6% and 18.6% of methylated patients and in 91.8% and 6% of unmethylated patients, respectively (p=0.0046). Patterns of failure were similar between the different treatment plans. Reduced target volumes were associated with significantly lower doses of 20-50 Gy to normal brain and hippocampi (p=0.0001). Conclusion Most of patients treated with standard chemioradiotherapy have in-field recurrences; however, an increased risk of distant recurrences occurs in methylated tumors. The use of target delineation using 1-cm CTV margin is associated with smaller volumes of normal brain and hippocampi irradiated to high doses, without significant changes in the pattern of failure. The impact of different target delineation in terms of efficacy and risk of late radiation-induced toxicity should be assessed prospectively.

Reduced RNA adenosine-to-inosine editing in hippocampus vasculature associated with Alzheimer's disease.

Alzheimer’s disease is the most common form of dementia and recent studies identify a type 1 interferon response in Alzheimer’s disease possibly driving neuro-inflammation and other Alzheimer’s disease pathologies. Loss of adenosine-to-inosine editing of endogenous Alu RNAs results in accumulation of Alu double-stranded RNAs, activation of double-stranded RNA sensors, and induction of interferon and nuclear factor kappa B regulated genes. Here, we investigated if changes in adenosine-to-inosine editing were associated with presence of Alzheimer’s disease in total prefrontal cortex, total hippocampus, cortex vasculature and hippocampus vasculature using available RNA sequencing files. We found similar levels of Alu RNA adenosine-to-inosine editing in cortex and cortex vasculature from individuals with Alzheimer’s disease or normal cognition at the time of death and brain donation. We found modest and substantial loss of adenosine-to-inosine editing in hippocampus and hippocampus vasculature, respectively, in Alzheimer’s disease relative to normal cognition and increased expression of interferon and nuclear factor kappa B regulated genes in hippocampus. Unedited Alu RNAs as found in Alzheimer’s disease hippocampus vasculature were potent innate immune activators while edited Alu RNAs as found in normal cognition hippocampus vasculature were weak innate immune activators. Taken together, our results support a model whereby loss of Alu RNA adenosine-to-inosine editing in hippocampus results in innate immune activation that may contribute to Alzheimer’s disease pathogenesis.

Gangliosidome of a Human Hippocampus in Temporal Lobe Epilepsy Resolved by High-Resolution Tandem Mass Spectrometry.

In this study, we developed a high-resolution tandem mass spectrometry (HR MS) approach to assess presumed changes in gangliosidome of a human hippocampus affected by temporal lobe epilepsy (TLE) in comparison with a normal hippocampus. Gangliosides, membrane glycolipids, are particularly diverse and abundant in the human brain, and participate in ion transport and modulation of neuronal excitability. Changes in structural ganglioside pattern potentially linked to TLE molecular pathogenesis have not been explored in detail. Aiming to characterize TLE-specific gangliosidome, we analyzed the native gangliosides purified from a human hippocampal tissue sample affected by TLE and a control hippocampus using HR MS. Marked differences of ganglioside expression were shown in TLE vs. control, particularly with respect to the sialylation degree of components, discovered as a characteristic feature of TLE. Another major finding is the occurrence of tetrasialofucogangliosides in TLE and species modified by either O-acetylation or CH3COO−. Structural analysis by higher-energy collisional dissociation (HCD) MS/MS gave rise to fragmentation patterns implying that the GQ1b (d18:1/18:0) isomer is specifically associated with TLE. Further investigation in a larger sample is needed in order to confirm the discovery of ganglioside structures specifically expressed in human TLE and to provide information on the probable role of gangliosides in the molecular events underlying seizures.

Integrated Analysis of Expression Profile and Potential Pathogenic Mechanism of Temporal Lobe Epilepsy With Hippocampal Sclerosis.

ObjectiveTo investigate the potential pathogenic mechanism of temporal lobe epilepsy with hippocampal sclerosis (TLE+HS) by analyzing the expression profiles of microRNA/ mRNA/ lncRNA/ DNA methylation in brain tissues.MethodsBrain tissues of six patients with TLE+HS and nine of normal temporal or parietal cortices (NTP) of patients undergoing internal decompression for traumatic brain injury (TBI) were collected. The total RNA was dephosphorylated, labeled, and hybridized to the Agilent Human miRNA Microarray, Release 19.0, 8 × 60K. The cDNA was labeled and hybridized to the Agilent LncRNA+mRNA Human Gene Expression Microarray V3.0,4 × 180K. For methylation detection, the DNA was labeled and hybridized to the Illumina 450K Infinium Methylation BeadChip. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. P-value < 0.05 and absolute fold change >2 were considered the threshold of differential expression data. Data analyses were performed using R and Bioconductor. BrainSpan database was used to screen for signatures that were not differentially expressed in normal human hippocampus and cortex (data from BrainSpan), but differentially expressed in TLE+HS’ hippocampus and NTP’ cortex (data from our cohort). The strategy “Guilt by association” was used to predict the prospective roles of each important hub mRNA, miRNA, or lncRNA.ResultsA significantly negative correlation (r < −0.5) was found between 116 pairs of microRNA/mRNA, differentially expressed in six patients with TLE+HS and nine of NTP. We examined this regulation network’s intersection with target gene prediction results and built a lncRNA-microRNA-Gene regulatory network with structural, and functional significance. Meanwhile, we found that the disorder of FGFR3, hsa-miR-486-5p, and lnc-KCNH5-1 plays a key vital role in developing TLE+HS.

P2X7-dependent constitutive Interleukin-1β release from pyramidal neurons of the normal mouse hippocampus: Evidence for a role in maintenance of the innate seizure threshold

Disruption of Interleukin-1β (IL-1β) signaling sensitized mice to convulsant stimuli, suggesting that this quintessential cytokine of the innate immune system contributes to maintenance of the innate seizure threshold (ST). However, much remains unknown about where and how IL-1β secretion occurs in the normal brain. This study examined the possibility that neurons of the hippocampus are key sources of constitutive IL-1β secretion and that the release from these cells is dependent on the purinoceptor, P2X7. It was posited that treatment with the P2X7 antagonist, JNJ-47965567 (JNJ), would cause IL-1β to accumulate in cells that produce it, and consequently, lower the ST. No IL-1β immunoreactivity was detected in any region of the hippocampal formation of mice treated with the JNJ vehicle, Sulfobutylether-β-cyclodextrin. In contrast, prominent immunoreactivity was discovered in the pyramidal neurons of the CA3 region 60 min after treatment with the P2X7 antagonist. Lower levels were found in CA1 neurons, and no immunoreactivity was detected in granule cells of the dentate gyrus. JNJ also increased IL-1β immunoreactivity in the cell bodies of hippocampal neurons in culture. Interestingly, JNJ potentiated bicuculline-induced Fos and COX-2 mRNA expression in the cultures and this was blocked by an NMDA receptor antagonist. Moreover, pentylenetetrazole-induced seizure severity and incidence of convulsions were increased in mice treated with JNJ and this resembled that observed with IL-1 signaling-deficient mice. Overall, the results from this study support the notion that constitutive P2X7-dependent IL-1β release from hippocampal pyramidal neurons contributes to maintenance of the ST in the normal brain, perhaps by modulating neuronal excitability. These findings may have implications for epilepsy, a brain disorder in which the ST is compromised.

Convolutional Neural Networks Enable Robust Automatic Segmentation of the Rat Hippocampus in MRI After Traumatic Brain Injury.

Registration-based methods are commonly used in the automatic segmentation of magnetic resonance (MR) brain images. However, these methods are not robust to the presence of gross pathologies that can alter the brain anatomy and affect the alignment of the atlas image with the target image. In this work, we develop a robust algorithm, MU-Net-R, for automatic segmentation of the normal and injured rat hippocampus based on an ensemble of U-net-like Convolutional Neural Networks (CNNs). MU-Net-R was trained on manually segmented MR images of sham-operated rats and rats with traumatic brain injury (TBI) by lateral fluid percussion. The performance of MU-Net-R was quantitatively compared with methods based on single and multi-atlas registration using MR images from two large preclinical cohorts. Automatic segmentations using MU-Net-R and multi-atlas registration were of excellent quality, achieving cross-validated Dice scores above 0.90 despite the presence of brain lesions, atrophy, and ventricular enlargement. In contrast, the performance of single-atlas segmentation was unsatisfactory (cross-validated Dice scores below 0.85). Interestingly, the registration-based methods were better at segmenting the contralateral than the ipsilateral hippocampus, whereas MU-Net-R segmented the contralateral and ipsilateral hippocampus equally well. We assessed the progression of hippocampal damage after TBI by using our automatic segmentation tool. Our data show that the presence of TBI, time after TBI, and whether the hippocampus was ipsilateral or contralateral to the injury were the parameters that explained hippocampal volume.

A unique subtype of ramified microglia associated with synapses in the rat hippocampus.

To date, a number of studies have reported the heterogeneity of activated microglia. However, there is increasing evidence suggests that ramified, so-called resting, microglia may also be heterogeneous, and they may play diverse roles in normal brain homeostasis. Here, we found that both 5D4 keratan sulfate epitope-positive (5D4+ ) and 5D4-negative (5D4- ) microglia coexisted in the hippocampus of normal rats, while all microglia were negative for the 5D4 epitope in the hippocampus of normal mice. We thus aimed to determine the potential heterogeneity of microglia related to the 5D4 epitope in the normal rat hippocampus. The optical disector analysis showed that the densities of 5D4+ microglia were higher in the stratum oriens of the CA3 region than in other layers and regions. Although both 5D4+ and 5D4- microglia exhibited a ramified morphology, the three-dimensional reconstruction analysis showed that the node numbers, end numbers, and complexity of processes were higher in 5D4+ than in 5D4- microglia. The linear discriminant analysis showed that 5D4+ and 5D4- microglia can be classified into distinct morphometric subtypes. The ratios of contact between synaptic boutons and microglial processes were higher in 5D4+ than in 5D4- microglia. The gene expressions of pro-inflammatory cytokine interleukin-1β and purinergic receptor P2Y12 (P2Y12 R) were higher in 5D4+ than in 5D4- microglia. Together, these results indicate that at least two different subtypes of ramified microglia coexist in the normal rat hippocampus and also suggest that 5D4+ microglia may represent a unique subtype associated with synapses.

Automated detection of hippocampal sclerosis: Comparison of a composite MRI-based index with conventional MRI measures

PurposeThis study aims to compare the performance of an MRI-based composite index (HSI) with conventional MRI-based measures in hippocampal sclerosis (HS) detection and postoperative outcome estimation. MethodsSeventy-two temporal lobe epilepsy (TLE) patients with pathologically confirmed HS and fifteen TLE patients without HS were included retrospectively. The T1-weighted and FLAIR images of these patients were processed with AccuBrain to quantify the hippocampal volume (HV) and the hippocampal FLAIR signal. The HSI index that considered both HV and hippocampal FLAIR signal was also calculated. Two experienced neuropathologists rated the HS severity with the resected tissue and reached an agreement for all cases. The asymmetry indices of the MRI measures were used to lateralize the sclerotic side, and the original MRI measures were applied to detect HS vs. normal hippocampi. Operating characteristic curve (ROC) analyses were performed for these predictions. We also investigated the sensitivity of the ipsilateral MRI measures in characterizing the pathological severity of HS and the associations of the MRI measures with postoperative outcomes (Engel class categories). ResultsWith the optimal cutoffs, the asymmetry indices of HSI and HV both achieved excellent performance in differentiating left vs. right HS (accuracy = 100 %), and the absolute value of the asymmetry index of HSI performed best in differentiating unilateral vs. bilateral HS (accuracy = 91.7 %). Regarding the detection of HS, HSI performed better in sensitivity (94.4 % vs. 87.5 %) while HV performed better in specificity (93.6 % vs. 89.4 %) when the contralateral site of unilateral HS and both sides of non-HS patients were considered as the normal reference, and HSI performed even better than HV when only both sides of non-HS patients were considered as the normal reference (AUC: 0.956 vs. 0.934, p = 0.038). The ipsilateral HSI presented the strongest association with the pathological rating of HS severity (r = 0.405, p < 0.001). None of the ipsilateral or contralateral MRI measures was associated with the postoperative outcomes. Among the asymmetry indices, only the absolute value of the asymmetry index of HV presented a significant association with the Engel classifications for the Year 2∼3 visit (r = -0.466, p = 0.004) or the latest visit with >1 year follow-up (r = -0.374, p = 0.003) while controlling for disease duration and follow-up duration. ConclusionThe HSI index and HV presented comparable good performance in HS detection, and HSI may have better sensitivity than HV in differentiating pathological HS severity. Higher magnitude of HV dissymmetry may indicate better post-surgical outcomes for HS patients.

CHARACTERIZATION OF HIPPOCAMPUS ON EPILEPTIC PATIENTS ON MRI USING TEXTURE ANALYSIS TECHNIQUES

The aim of this study was to characterize the hippocampus in Sudanese epileptic patients in MR images using image texture analysis techniques in order to differentiate hippocampus between the normal and epileptic patient. There were two groups of the patients were examined by using Signal-GE 1.5Tesla MR Scanner which was used with patients with known epilepsy and normal T1 weighted brain. MRI finding patients, 101 and 105 patients respectively examined in period from December 2017- March 2018, where the variables of the study were MRI images entered to the IDL program as input for further analysis, using window 3*3 the images texture was extracted from hippocampus (head, body and tail) that include, mean, STD, variance, energy, and entropy then the comparison was made to differentiate between the normal and abnormal hippocampus. The extracted feature classified using linear discriminate analysis. The classification score function is used to classify the hippocampus classes was as flows:&#x0D; Epileptic= (.271×mean) + (.026×variance) + (7.475× Part) -32.134&#x0D; Normal= (.240×mean) + (.052×variance) + (2.960× Part) -13.684&#x0D; The study confirmed that it’s possible to differentiate between normal and epileptic hippocampus body, head, and tail in sagittal section texturally. The result showed that the classification result is best in the tail where higher classification accuracy will be achieved followed by body and then head.

Deep learning-based automatic delineation of the hippocampus by MRI: geometric and dosimetric evaluation

BackgroundWhole brain radiotherapy (WBRT) can impair patients’ cognitive function. Hippocampal avoidance during WBRT can potentially prevent this side effect. However, manually delineating the target area is time-consuming and difficult. Here, we proposed a credible approach of automatic hippocampal delineation based on convolutional neural networks.MethodsReferring to the hippocampus contouring atlas proposed by RTOG 0933, we manually delineated (MD) the hippocampus on the MRI data sets (3-dimensional T1-weighted with slice thickness of 1 mm, n = 175), which were used to construct a three-dimensional convolutional neural network aiming for the hippocampus automatic delineation (AD). The performance of this AD tool was tested on three cohorts: (a) 3D T1 MRI with 1-mm slice thickness (n = 30); (b) non-3D T1-weighted MRI with 3-mm slice thickness (n = 19); (c) non-3D T1-weighted MRI with 1-mm slice thickness (n = 11). All MRIs confirmed with normal hippocampus has not been violated by any disease. Virtual radiation plans were created for AD and MD hippocampi in cohort c to evaluate the clinical feasibility of the artificial intelligence approach. Statistical analyses were performed using SPSS version 23. P < 0.05 was considered significant.ResultsThe Dice similarity coefficient (DSC) and Average Hausdorff Distance (AVD) between the AD and MD hippocampi are 0.86 ± 0.028 and 0.18 ± 0.050 cm in cohort a, 0.76 ± 0.035 and 0.31 ± 0.064 cm in cohort b, 0.80 ± 0.015 and 0.24 ± 0.021 cm in cohort c, respectively. The DSC and AVD in cohort a were better than those in cohorts b and c (P < 0.01). There is no significant difference between the radiotherapy plans generated using the AD and MD hippocampi.ConclusionThe AD of the hippocampus based on a deep learning algorithm showed satisfying results, which could have a positive impact on improving delineation accuracy and reducing work load.

Outcomes of hippocampus-sparing lesionectomy for temporal lobe epilepsy and the significance of intraoperative hippocampography

ObjectivesWe investigated hippocampal-sparing lesionectomy (HSL) outcomes in temporal lobe epilepsy (TLE) and the significance of high-frequency oscillations (HFOs) detected by hippocampography in HSL. MethodsWe retrospectively reviewed data from patients who underwent HSL for lesional TLE. Patients were included when MRI confirmed (i) a lesion limited to the temporal lobe with normal hippocampi preoperatively and (ii) hippocampal integrity postoperatively. Factors possibly related to outcomes were collected. Intraoperative hippocampography was reviewed, and spikes, ripples, and fast ripples were marked. Seizure outcomes were tracked ≥ 2 years. Postoperative neuropsychological tests were performed and analyzed. ResultsWe included 67 patients (35 males/32 females, median age at surgery 28 years, 57 seizure-free). Complete resection was significantly associated with being seizure-free without aura, an outcome achieved by 32 (69.6%) patients with complete resection vs 1 (12.5%) with incomplete resection (p = 0.004). Spikes/ripples/fast ripples appeared frequently in the hippocampus, occurring in 86.4%/82.4%/75.0% of cases before resection and 76.7%/78.1%/63.0% after resection. The presence and rate were unconnected to seizure outcome. Postoperative neuropsychological outcomes in intelligence and visual memory improved overall. ConclusionsHSL in lesional TLE can produce satisfactory seizure and cognitive outcomes. Intraoperative hippocampography-guided resection of apparently normal hippocampi should be performed cautiously and might not be necessary. SignificanceThis study provided evidence in decision making for patients with lesional TLE with a radiologically normal hippocampus.

Apoptosis in hippocampal tissue induced by oxidative stress in testosterone deprived male rats

The testosterone decline is one of the potential causes of oxidative stress-induced anxiety and depressive behaviors, and cognitive impairment induces irreversible neuronal damage, which is not clearly understood. The orchidectomized rat model was used; the hippocampal neurons and anxiety behavior were analyzed. Adult male albino rats were divided into control and orchidectomy (ORX) groups, orchidectomy (ORX + T), and normal (Cont + T) groups. Testosterone propionate was used as a testosterone supplement. The anxiety and depressive-like behavior observed in ORX animals in the open field (OF) and elevated plus-maze experiments were effectively overturned in the ORX + T group. Studies on isolated hippocampus showed reduced antioxidant enzymes (SOD, CAT, and glutathione (GSH) compounds), increased lipid peroxidation (LPO), elevated caspase3, and reduced anti-apoptotic protein Bcl-2, and increased apoptotic nuclei in TUNEL staining of the hippocampus in the ORX rats. These observations indicate free radical-mediated neural damage. Testosterone presence promoted the antioxidant defense system and restored normal pyramidal neuron morphology in ORX + T. This study confirms that testosterone is indispensable in the normal adult hippocampus and deficiency seems to be a potential risk factor for neurodegenerative disorders. Besides, androgen appears to be a possible therapeutic strategy for treating depression/neurodegenerative diseases in aging men.