Epilepsy is a common cerebral disease, and may cause sudden death. Although electric activity study of epileptic brain had been emphasized in the past, the neuropathological study of epilepsy has become a main focus in clinical and forensic medicine recently. This article reviews the recent progress in neuropathology of epilepsy including developmental disorder, abnormal tumoral proliferation, hippocampal sclerosis, dual pathological alteration, and mossy fiber sprouting. Its significance in forensic medicine, particularly for the diagnosis of sudden unexpected death in epilepsy, is discussed.
Brain/pathology* ; Brain Neoplasms/pathology* ; Cause of Death ; Death, Sudden/etiology* ; Epilepsy/physiopathology* ; Forensic Pathology ; Hippocampus/pathology* ; Humans ; Malformations of Cortical Development/pathology* ; Sclerosis/pathology*

Brain Stem/pathology* ; Death, Sudden/etiology* ; Fatal Outcome ; Humans ; Intracranial Hemorrhages/mortality* ; Leukemia/pathology*

Ischemic stroke caused by intracranial vascular occlusion has become increasingly prevalent with considerable mortality and disability, which gravely burdens the global economy. Current relatively effective clinical treatments are limited to intravenous alteplase and thrombectomy. Even so, patients still benefit little due to the short therapeutic window and the risk of ischemia/reperfusion injury. It is therefore urgent to figure out the neuronal death mechanisms following ischemic stroke in order to develop new neuroprotective strategies. Regarding the pathogenesis, multiple pathological events trigger the activation of cell death pathways. Particular attention should be devoted to excitotoxicity, oxidative stress, and inflammatory responses. Thus, in this article, we first review the principal mechanisms underlying neuronal death mediated by these significant events, such as intrinsic and extrinsic apoptosis, ferroptosis, parthanatos, pyroptosis, necroptosis, and autophagic cell death. Then, we further discuss the possibility of interventions targeting these pathological events and summarize the present pharmacological achievements.
Brain Ischemia/pathology* ; Cell Death ; Humans ; Ischemic Stroke ; Reperfusion Injury/pathology* ; Stroke/pathology* ; Tissue Plasminogen Activator/therapeutic use*

AIMTo investigate the effects of the duration of cerebral ischemic preconditioning(CIP) and interval between CIP and the subsequent ischemic insult on the protection of CIP against delayed neuronal death (DND) in the CA1 hippocampus normally induced by brain ischemic insult.

METHODSFour-vessel occlusion cerebral ischemic model of rats (54) was used. The brain of the rats was sectioned and stained with thionin to show DND in the CA1 hippocampus.

RESULTSNo DND was found in the hippocampus of the rats subjected to sham operation and CIP, in which 3 min cerebral ischemic preconditioning was performed. Obvious destruction of the CA1 hippocampus was found in brain ischemic insult group, in which histological (HG) was 2-3 in 6 min and 10 min ischemia subgroups and grade 3 in 15 min ischemia subgroup. In CIP + brain ischemic insult group, no obvious neuronal damage was found in 3 min-3d-6 min (CIP for 3 min was followed by a brain ischemic insult for 6 min at an interval of 3 d, the same as the following) and 3 min-3 d-10 min groups, indicating that CIP effectively protected neurons of the CA1 hippocampus against DND normally induced by ischemic insult for 6 or 10 min. However, in 3 min-1 d-10 min and 3 min-3 d-15 min groups, the protective effect of CIP was lower than that in the 3 min-3 d-10 min group. The quantitative analysis of the protective effect of CIP on the CA1 hippocampal neurons showed that there was no significant difference in protecting number and protecting index between 3 min-3 d-6 min and 3 min-3 d-10 min groups (P > 0.05). However, the growth index in 3 min-3 d-10 min group was obvious larger than that in 3 min-3 d-6 min (P < 0.05).

CONCLUSIONAlthough the protective effects of CIP in 3 min-3 d-6 min and 3 min-3 d-10 min groups were similar, the protective effect of CIP in 3 min-3 d-10 min group was sensitively found. Maximal protective potential of CIP could be induced when using the time parameters of 3 min-3 d-10 min to establish the model of global cerebral ischemic tolerance.

Animals ; Brain Injuries ; pathology ; prevention & control ; Brain Ischemia ; pathology ; prevention & control ; Cell Death ; Hippocampus ; pathology ; Ischemic Preconditioning ; Male ; Neurons ; pathology ; Rats ; Rats, Wistar ; Time Factors

A retrospective analysis of brain metastasis with respect to the pathology, hydrocephalus, cause of death, survival time and therapeutic modality was carried out in 47 cases. The duration of survival after CNS metastasis far less depends on the primary tumor than the latent interval between the onset of first symptom from primary tumor and CNS metastasis dose. And death was attributable to the CNS metastases in at least 5.3% of these cases. Surgery and radiotherapy but chemotherapy were included in this study. Radiotherapy had significant effects on prolongation of survival. The surgery plus postoperative whole brain radiotherapy had the longest survivals than the other treatment modalities. The authors recommend guidelines for surgical resection, usually followed by radiotherapy:in cases which have good general condition enough to tolerate general anesthesia without any acute general morbidness, (1) single surgically accessible brain metastasis, (2) an incapacitating or large metastasis even when the tumor is not solitary, (3) uncertain primary cancer, (4) posterior fossa, especially cerebellar hemispheric metastasis. It seems that the presence of metastasis else where in the body should not exclude the case as a surgical candidate.
Anesthesia, General ; Brain* ; Cause of Death ; Drug Therapy ; Hydrocephalus ; Neoplasm Metastasis* ; Pathology ; Prognosis* ; Radiotherapy ; Retrospective Studies*

A retrospective analysis of brain metastasis with respect to the pathology, hydrocephalus, cause of death, survival time and therapeutic modality was carried out in 47 cases. The duration of survival after CNS metastasis far less depends on the primary tumor than the latent interval between the onset of first symptom from primary tumor and CNS metastasis dose. And death was attributable to the CNS metastases in at least 5.3% of these cases. Surgery and radiotherapy but chemotherapy were included in this study. Radiotherapy had significant effects on prolongation of survival. The surgery plus postoperative whole brain radiotherapy had the longest survivals than the other treatment modalities. The authors recommend guidelines for surgical resection, usually followed by radiotherapy:in cases which have good general condition enough to tolerate general anesthesia without any acute general morbidness, (1) single surgically accessible brain metastasis, (2) an incapacitating or large metastasis even when the tumor is not solitary, (3) uncertain primary cancer, (4) posterior fossa, especially cerebellar hemispheric metastasis. It seems that the presence of metastasis else where in the body should not exclude the case as a surgical candidate.
Anesthesia, General ; Brain* ; Cause of Death ; Drug Therapy ; Hydrocephalus ; Neoplasm Metastasis* ; Pathology ; Prognosis* ; Radiotherapy ; Retrospective Studies*

Amniotic fluid embolism, one of the leading causes of maternal death, is a rare event, however, it can cause maternal death and neonatal morbidity when it unrecognized and untreated effectively. Its pathogenesis is unclear and clinical presentations are variable without standardized means of confirming diagnosis. We experienced one case of neonatal hypoxic ischemic encephalopathy possibly due to maternal amniotic fluid embolism, which was diagnosed by brain MRI, EEG and maternal uterine pathology. We report this case with a brief review of literatures.
Amniotic Fluid* ; Brain ; Diagnosis ; Electroencephalography ; Embolism, Amniotic Fluid* ; Female ; Hypoxia-Ischemia, Brain* ; Magnetic Resonance Imaging ; Maternal Death ; Pathology ; Pregnancy

Sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Additionally, potential pathomechanisms for SUDEP is unknown, but it is very probable that cardiac arrhythmia during and between seizures, electrolyte disturbances, arrhythmogenic drugs or transmission of epileptic activity via the autonomic nervous system to the heart may play a potential role. Quite interestingly, clinical and experimental data have shown that physical activity can decrease seizure frequency, as well as lead to improved cardiovascular health in patients with epilepsy. Based on these facts, the purpose of this article is to review the body of literature of the possible contribution of physical exercise to the SUDEP prevention in a comprehensive manner.
Animals ; Brain ; metabolism ; pathology ; Death, Sudden ; etiology ; prevention & control ; Epilepsy ; pathology ; physiopathology ; Gene Expression Regulation ; Humans ; Motor Activity ; physiology

Sudden cardiac death(SCD) from early myocardial ischemia is often lack of typically morphological findings and clinical manifestation, thus cases of SCD may be suspected as criminal cases. It is necessary to clarify the cause of death, which is significance for medico-legal investigation. This article reviewed the latest advancement in the studies on the application of inorganic ions, CK-MB, cTn, ANP and BNP for certification of death from SCD in order to provide a practical way for diagnosis of SCD in forensic pathology.
Atrial Natriuretic Factor/metabolism* ; Autopsy ; Biomarkers/metabolism* ; Calcium/metabolism* ; Cause of Death ; Creatine Kinase, MB Form/metabolism* ; Death, Sudden, Cardiac/pathology* ; Forensic Pathology ; Humans ; Myocardial Infarction/pathology* ; Myocardial Ischemia/pathology* ; Myocardium/pathology* ; Natriuretic Peptide, Brain/metabolism* ; Troponin/metabolism*

Changes in morphology, immunophenotypes and proliferative activity of neuroglia are key features in most forms of CNS pathology. We compared proliferative activity of neuroglial cells in response to two different types of brain injury induced by medial forebrain bundle (MFB) axotomy. In the cannula track where acute necrosis occurs due to mechanical lesion caused by cannula inserted to incise the MFB, many BrdU-immunoreactive (ir) cells appeared around the cannula track already at 1 day post-lesion (1 dpl). Their number significantly increased by 7 dpl and then decreased, but considerable number of BrdU-ir cells was still found at 14 dpl. Some of the BrdU-ir cells were double-labeled with either OX-42 or GFAP. This finding suggests that both microglia and astrocytes are activated and proliferate immediately after the mechanical damage, and the proliferative activity is maintained in a considerable number of these cells by 14 dpl. In general, the main cell type showing BrdU immunoreactivity was amoeboid microglia within the necrotic zone immediately surrounding the cannula track, and was astrocytes in the periphery of the necrotic zone more or less apart from the cannula track. Previously, we reported that MFB axotomy induces apoptosis of dopaminergic (DA) neurons in the substantia nigra (SN). In the SN where axotomized DA neurons undergo apoptosis, only a few BrdU-ir cells were found at 1 dpl. Their number increased gradually from 3 dpl and peaked at 7 dpl, then significantly reduced at 14 dpl. Most of them were double-labeled with OX -42-positive ramified microglia but not with GFAP. This data indicates that microglia but not astrocyte are the cell type that proliferate in response to apoptotic neuronal cell death, and their morphology and proliferative activity are different from those observed in the cannula track. Meanwhile, in the both cannula track and SN, some BrdU-ir cells were thought to be neither GFAP-positive nor OX-42-positive, and thus they were presumed to be infiltrated peripheral immune cells. These results demonstrate that different types of neuronal cell death are accompanied with different neurogilal proliferative activities.
Apoptosis ; Astrocytes ; Axotomy* ; Brain Injuries ; Bromodeoxyuridine ; Catheters ; Cell Death ; Medial Forebrain Bundle* ; Microglia ; Necrosis ; Neuroglia ; Neurons ; Pathology ; Substantia Nigra