Characteristics of Visual Evoked Potential in Different Parts of Visual Impairment. / 不同部位损伤致视力障碍的视觉诱发电位特征.

OBJECTIVES: To study the quantitative and qualitative differences of visual evoked potential (VEP) in monocular visual impairment after different parts of visual pathway injury. METHODS: A total of 91 subjects with monocular visual impairment caused by trauma were selected and divided into intraocular refractive media-injury group (eyeball injury group for short), optic nerve injury group, central nervous system injury and intracranial combined injury group according to the injury cause and anatomical segment. Pattern Reversal visual evoked potential (PR-VEP) P100 peak time and amplitude, Flash visual evoked potential (F-VEP) P2 peak time and amplitude were recorded respectively. SPSS 26.0 software was used to analyze the differences of quantitative (peak time and amplitude) and qualitative indexes (spatial frequency sweep-VEP acuity threshold, and abnormal waveform category and frequency) of the four groups. RESULTS: Compared with healthy eyes, the PR-VEP P100 waveforms of the intraocular eyeball injury group and the F-VEP P2 waveforms of the optic nerve group showed significant differences in prolonged peak time and decreased amplitude in injured eyes (P<0.05). The PR-VEP amplitudes of healthy eyes were lower than those of injured eyes at multiple spatial frequencies in central nervous system injury group and intracranial combined injury group (P<0.05).The amplitude of PR-VEP in patients with visual impairment involving central injury was lower than that in patients with eye injury at multiple spatial frequencies. The frequency of VEP P waveforms reaching the threshold of the intraocular injury group and the optic nerve injury group were siginificantly different from the intracranial combined injury group, respectively(P<0.008 3), and the frequency of abnormal reduction of VEP amplitude of threshold were significantly different from the central nervous system injury group, respectively(P<0.008 3). CONCLUSIONS: VEP can distinguish central injury from peripheral injury, eyeball injury from nerve injury in peripheral injury, but cannot distinguish simple intracranial injury from complex injury, which provides basic data and basis for further research on the location of visual impairment injury.

Salubrinal offers neuroprotection through suppressing endoplasmic reticulum stress, autophagy and apoptosis in a mouse traumatic brain injury model.

Traumatic brain injury (TBI) is a complex injury that can cause severe disabilities and even death. TBI can induce secondary injury cascades, including but not limited to endoplasmic reticulum (ER) stress, apoptosis and autophagy. Although the investigators has previously shown that salubrinal, the selective phosphatase inhibitor of p-eIF2α, ameliorated neurologic deficits in murine TBI model, the neuroprotective mechanisms of salubrinal need further research to warrant the preclinical value. This study was undertaken to characterize the effects of salubrinal on cell death and neurological outcomes following TBI in mice and the potential mechanisms. In the current study, ER stress-related proteins including p-eIF2α, GRP78 and CHOP showed peak expressions both in the cortex and hippocampus from day 2 to day 3 after TBI, indicating ER stress was activated in our TBI model. Immunofluorescence staining showed that CHOP co-located NeuN-positive neuron, GFAP-positive astrocyte, Iba-1-positive microglia, CD31-positive vascular endothelial cell and PDGFR-ß-positive pericyte in the cortex on day 2 after TBI, and these cells mentioned above constitute the neurovascular unit (NVU). We also found TBI-induced plasmalemma permeability, motor dysfunction, spatial learning and memory deficits and brain lesion volume were alleviated by continuous intraperitoneal administration of salubrinal post TBI. To investigate the underlying mechanisms further, we determined that salubrinal suppressed the expression of ER stress, autophagy and apoptosis related proteins on day 2 after TBI. In addition, salubrinal administration decreased the number of CHOP+/TUNEL+ and CHOP+/LC3+ cells on day 2 after TBI, detected by immunofluorescence. In conclusion, these data imply that salubrinal treatment improves morphological and functional outcomes caused by TBI in mice and these neuroprotective effects may be associated with inhibiting apoptosis, at least in part by suppressing ER stress-autophagy pathway.

IN VIVO EFFECT OF GUIDING-HERB RADIX PLATYCODONIS AND RADIX CYATHULAE ON PAEONIFLORIN PHARMACOKINETICS OF XUEFU ZHUYU TANG IN RATS.

BACKGROUND: Xuefu Zhuyu Tang (XFZYT), first recorded in Correction of Errors in Medical Works by Qing-ren Wang, has been proven reliable and effective for curing various diseases such as atherosclerosis, hypertension, hyperlipidemia, and angina pectoris. It consists of 11 herbs and two of them, Radix platycodonis and Radix cyathulae, have been traditionally considered as guiding herbs and deeply valued by tens of millions of Chinese medicine practitioners. Do Radix platycodonis and Radix cyathulae affect the pharmacokinetics of the effective constituent-paeoniflorin of XFZYT? If yes, in what way? This study aims to answer these questions. MATERIALS AND METHODS: The medicinal solutions of XFZYT, XFZYT without Radix platycodonis (XFZYT-JG), XFZYT without Radix cyathulae (XFZYT-NX), and XFZYT without Radix platycodonis and Radix cyathulae (XFZYT-JG-NX) were prepared and administrated to rats in the normal group and the blood-stasis model group by gavage, respectively. The blood samples of rats in the normal group were obtained 5, 10, 15, 20, 30, 45, 60, 120, and 240 minutes after gavage; whereas the blood samples of rats in the blood-stasis model group were obtained 10, 15, 20, 30, 45, 90, 150, and 240 minutes after gavage. Biological samples were processed; the assays of specificity, precision, linearity, intra-day and inter-day precisions, recovery and stability were conducted; high performance liquid chromatography was performed to detect paeoniflorin content; and DAS software was adopted to generate pharmacokinetic parameters. Mobile phase was composed of acetonitrile and water (16:84), detection wavelength was 230 nm, and riboflavin was set as internal standard substance. RESULTS: The pharmacokinetic parameters of the rats in the normal group after oral gavage of XFZYT, XFZYT-JG, XFZYT-NX, and XFZYT-JG-NX were Cmax = (0.363±0.248, 0.065±0.020, 0.099±0.033, 0.099±0.020) mg/L, Tmax = (0.276±0.084, 0.583±0.342, 0.555±0.228, 0.317±0.033)h, t1/2 = (0.501±0.241, 1.021±0.522, 0.853±0.377, 1.227±0.402) h; and AUC0-∞ = (0.381±0.415, 0.13±0.085, 0.166±0.066, 0.185±0.059) mg/L·h.; whereas the pharmacokinetic parameters for the rats in the blood-stasis model group after oral gavage of XFZYT, XFZYT-JG, XFZYT-NX, and XFZYT-JG-NX were Cmax = (0.315±0.153, 0.215±0.044, 0.228±0.056, 0.248±0.09) mg/L, Tmax = (0.5±0, 0.667±0.129, 0.5±0, 0.542±0.102) h, t1/2 = (0.408±0.146, 0.813±0.135, 0.708±0.383, 0.741±0.173) h, and AUC0-∞ = (0.306±0.157, 0.408±0.136, 0.368±0.159, 0.381±0.246) mg/L·h. CONCLUSION: The guiding herbs, Radix platycodonis and Radix cyathulae, significantly increased the absorption amount and rate of paeoniflorin in XFZYT, and accelerated its elimination from the blood.

Caspr Controls the Temporal Specification of Neural Progenitor Cells through Notch Signaling in the Developing Mouse Cerebral Cortex.

The generation of layer-specific neurons and astrocytes by radial glial cells during development of the cerebral cortex follows a precise temporal sequence, which is regulated by intrinsic and extrinsic factors. The molecular mechanisms controlling the timely generation of layer-specific neurons and astrocytes remain not fully understood. In this study, we show that the adhesion molecule contactin-associated protein (Caspr), which is involved in the maintenance of the polarized domains of myelinated axons, is essential for the timing of generation of neurons and astrocytes in the developing mouse cerebral cortex. Caspr is expressed by radial glial cells, which are neural progenitor cells that generate both neurons and astrocytes. Absence of Caspr in neural progenitor cells delays the production cortical neurons and induces precocious formation of cortical astrocytes, without affecting the numbers of progenitor cells. At the molecular level, Caspr cooperates with the intracellular domain of Notch to repress transcription of the Notch effector Hes1. Suppression of Notch signaling via a Hes1 shRNA rescues the abnormal neurogenesis and astrogenesis in Caspr-deficient mice. These findings establish Caspr as a novel key regulator that controls the temporal specification of cell fate in radial glial cells of the developing cerebral cortex through Notch signaling.

IL-33 Exerts Neuroprotective Effect in Mice Intracerebral Hemorrhage Model Through Suppressing Inflammation/Apoptotic/Autophagic Pathway.

Interleukin-33 (IL-33) is a recently identified member of the IL-1 family that exerts biologic functions by binding to a heterodimer composed of IL-1 receptor-related protein ST2L and IL-1RAcP. However, the role of IL-33 and whether IL-33 accounts for inflammation, apoptotic, and autophagic neuropathology after intracerebral hemorrhage (ICH) are not clear. Here, we established a mouse ICH model in this study, to determine the role of IL-33 and explore the underlying mechanism. Male mice were subjected to an infusion of type IV collagenase/saline into the left striatum to induce ICH/sham model. IL-33, soluble ST2 (sST2), or saline were also administered by a single intracerebroventricular (i.c.v.) injection, respectively. The results showed that the expression level of IL-33 markedly decreased within 6 h and reached the valleys at 6 and 72 h after ICH vs. sham group. In parallel, ST2L (a transmembrane form receptor of IL-33) significantly increased within 6 h and reached the peaks at 6 h and 24 h after ICH vs. sham group. In addition, administration of IL-33 alleviated cerebral water contents, reduced the number of PI- and TUNEL-positive cells, and improved neurological function after ICH. Moreover, IL-33 treatment apparently suppressed the expression of pro-inflammation cytokines IL-1ß and TNF-α, evidently increased Bcl-2 but decreased cleaved-caspase-3, and obviously decreased the levels of autophagy-associated proteins LC3-II and Beclin-1 but maintained P62 at high level after ICH. On the contrary, treatment with sST2, a decoy receptor of IL-33, exacerbated ICH-induced brain damage and neurological dysfunction by promoting apoptosis, and enhancing autophagic activity. In conclusion, IL-33 provides neuroprotection through suppressing inflammation, apoptotic, and autophagic activation in collagenase-induced ICH model.

IL-33 Provides Neuroprotection through Suppressing Apoptotic, Autophagic and NF-κB-Mediated Inflammatory Pathways in a Rat Model of Recurrent Neonatal Seizure.

Interleukin-33 (IL-33) is a novel identified chromatin-associated cytokine of IL-1 family cytokines. It signals through a heterodimer comprised of ST2L and IL-1RAcp, and plays a crucial role in many diseases. However, very little is known about the role and underlying intricate mechanisms of IL-33 in recurrent neonatal seizure (RNS). To determine whether IL-33 plays an important regulatory role, we established a neonatal seizure model in this study. Rats were subjected to recurrent seizures induced by inhaling volatile flurothyl. Recombinant IL-33 or PBS were also administered by intraperitoneally (IP) before surgery, respectively. Here, our current results indicated that RNS contributed to a significant reduction in IL-33 and its specific receptor (ST2L) expressions in cortex. While, in hippocampus, RNS induced an increase in IL-33 and ST2L evidently, compared with Sham group. After injection with IL-33, however, a remarkable increase in total IL-33 was detected both in brain cortex and hippocampus. In addition, IL-33 was mainly co-localized in the nuclear of GFAP+ astrocytes and the cytoplasm of the Iba-1+ microglia and IL-33+/NeuN+ merged cells. In parallel, ST2L was expressed mainly in the membrane of GFAP+ astrocytes, Iba-1+ microglia and NeuN+ neurons, respectively. Furthermore, administration of IL-33 improved RNS-induced behavioral deficits, promoted bodyweight gain, and ameliorated spatial learning and memory ability. Moreover, IL-33 pretreatment blocked the activation of NF-κB, resisted inflammatory cytokines IL-1ß and TNF-α increase, as well as suppressed apoptosis and autophagy activation after RNS. Collectively, IL-33 provides potential neuroprotection through suppressing apoptosis, autophagy and at least in part by NF-κB-mediated inflammatory pathways after RNS.

[Research Progress of Event-related Potential in Mild Cognitive Impairment].

Mild cognitive impairment caused by craniocerebral trauma is the key points and difficulties in judicial authentication. This article has comparative analysis of each mode of event-related potential (classical Oddball, Eriksen flanker task and so on), which can provide a more objective method for such craniocerebral trauma cases in clinical forensic judicial authentication.

Mismatch negativity, social cognition, and functional outcomes in patients after traumatic brain injury.

Mismatch negativity is generated automatically, and is an early monitoring indicator of neuronal integrity impairment and functional abnormality in patients with brain injury, leading to decline of cognitive function. Antipsychotic medication cannot affect mismatch negativity. The present study aimed to explore the relationships of mismatch negativity with neurocognition, daily life and social functional outcomes in patients after brain injury. Twelve patients with traumatic brain injury and 12 healthy controls were recruited in this study. We examined neurocognition with the Wechsler Adult Intelligence Scale-Revised China, and daily and social functional outcomes with the Activity of Daily Living Scale and Social Disability Screening Schedule, respectively. Mismatch negativity was analyzed from electroencephalogram recording. The results showed that mismatch negativity amplitudes decreased in patients with traumatic brain injury compared with healthy controls. Mismatch negativity amplitude was negatively correlated with measurements of neurocognition and positively correlated with functional outcomes in patients after traumatic brain injury. Further, the most significant positive correlations were found between mismatch negativity in the fronto-central region and measures of functional outcomes. The most significant positive correlations were also found between mismatch negativity at the FCz electrode and daily living function. Mismatch negativity amplitudes were extremely positively associated with Social Disability Screening Schedule scores at the Fz electrode in brain injury patients. These experimental findings suggest that mismatch negativity might efficiently reflect functional outcomes in patients after traumatic brain injury.

[Correlation of daily living activities with location and severity of traumatic brain injury].

OBJECTIVE: To study the correlation of daily living activities with location and severity of trau- matic brain injury (TBI) and to provide a theoretical basis for improving the accuracy of expert opinion. METHODS: Five hundred and one cases of patients with TBI were selected. Detailed records included following: pre-injury situation, location and severity of injury, treatment and education. Daily living activi- ties scale (Barthel index) was applied to test the subjects' daily living activities. The relevance among location and severity of TBI and Barthel index was statistically analyzed. RESULTS: In mild TBI group, there was no significant difference in Barthel index among each location (P>0.05). In moderate TBI group, there were significant differences in Barthel index between subarachnoid hemorrhage and cerebral lobe injury, also between parietal, occipital lobes injury and frontal lobe injury, parietal, occipital lobes injury and temporal lobe (P<0.05), respectively, whereas no significant difference in Barthel index between frontal lobe injury and temporal lobe injury (P>0.05). In severe TBI, there were significant differences in Barthel index between every two different locations (P<0.05). CONCLUSION: There is some correlation between the location of TBI and Barthel index, which provides an important reference value for analyzing and determining daily living activities after TBI.

Lipoxin A4 attenuates brain damage and downregulates the production of pro-inflammatory cytokines and phosphorylated mitogen-activated protein kinases in a mouse model of traumatic brain injury.

The present study was designed to investigate the effects of lipoxin A4 (LXA4) on traumatic brain injury (TBI) and to analyze the possible mechanism. Outcome parameters consist of blood-brain barrier (BBB) breakdown, brain edema and lesion volume. Using western blot and quantitative real-time PCR, we examined the levels of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6) and activation of mitogen-activated protein kinases (MAPKs) (including ERK, JNK, p38) following TBI. To investigate the cell types in which the LXA4 receptor (ALXR) staining was localized, brain sections pulsed with ALXR were subjected to immunofluorescence staining with antibodies against cell type-specific antigens. Our findings show that LXA4 decreases BBB permeability, attenuates brain edema, and reduces TBI-induced lesion volume. In addition, LXA4 inhibits TBI-induced elevation of mRNA and protein levels of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6). In the injured cortex at 24h post-TBI, the phosphorylated-ERK (p-ERK) and -JNK (p-JNK), but not -p38 (p-p38) levels were increased. The p-ERK and p-JNK production were attenuated by their respective inhibitors (PD98059 and SP600125), as well as LXA4. Moreover, ALXR was found to label more GFAP positive cells, whereas few CD11b-positive cells were labeled by ALXR within the layers of the injured cortex at 24h post-TBI. The activation of ALXR in astrocytes was partially enhanced by LXA4 treatment. Taken together, these data indicate that TBI activates pro-inflammatory cytokines, the MAPK pathways together with ALXR in astrocytes, and these mechanisms may be exploited by pharmacological interventions.

Therapeutic effect of SN50, an inhibitor of nuclear factor-κB, in treatment of TBI in mice.

NF-κB upregulation has been demonstrated in neurons and glial cells in response to experimental injury and neuropathological disorders, where it has been related to both neurodegenerative and neuroprotective activities. It has been generally recognized that NF-κB plays important roles in the regulation of apoptosis and inflammation as well as innate and adaptive immunity. However, the regulatory mechanism of NF-κB in apoptosis remained to be determined. The present study sought to first investigate the effect of a NF-κB inhibitor SN50, which inhibits NF-κB nuclear translocation, on cell death and behavioral deficits in our mice traumatic brain injury (TBI) models. Additionally, we tried to elucidate the possible mechanisms of the therapeutic effect of SN50 through NF-κB regulating apoptotic and inflammatory pathway in vivo. Encouragingly, the results showed that pretreatment with SN50 remarkably attenuated TBI-induced cell death (detected by PI labeling), cumulative loss of cells (detected by lesion volume), and motor and cognitive dysfunction (detected by motor test and Morris water maze). To analyze the mechanism of SN50 on cell apoptotic and inflammatory signaling pathway, we thus assessed expression levels of TNF-α, cathepsin B and caspase-3, Bid cleavage and cytochrome c release in SN50-pretreated groups compared with those in saline vehicle groups. The results imply that through NF-κB/TNF-α/cathepsin networks SN50 may contribute to TBI-induced extrinsic and intrinsic apoptosis, and inflammatory pathways, which partly determined the fate of injured cells in our TBI model.

Poloxamer 188 attenuates in vitro traumatic brain injury-induced mitochondrial and lysosomal membrane permeabilization damage in cultured primary neurons.

Acute membrane damage due to traumatic brain injury (TBI) is a critical precipitating event. However, the subsequent effects of the mechanical trauma, including mitochondrial and lysosomal membrane permeability (MOMP and LMP) remain elusive. The main objective of the current study was to assess the role of a putative membrane-resealing agent poloxamer 188 (P188) in MOMP and LMP in response to a well-defined mechanical insult. Using an in vitro cell shearing device (VCSD), mechanical injury resulted in immediate disruption of membrane integrity in cultured primary neurons, and neurons were treated with P188 or a cathepsin B inhibitor (CBI) after VCSD 10 min. The protective effect of P188 on cultured primary neurons was first detected visually with a light microscope, and measured by MTT assay and LDH assay. The validity of monitoring changes in mitochondrial membrane potential (ΔΨm) was measured by JC-1 staining, and Western blot for cytochrome c and truncated Bid (tBid) in purified mitochondria was also performed. In addition, lysosomal integrity was detected by blotting for cathepsin B and tBid in purified lysosomes. Our results showed post-injury P188 treatment moderated the dissipation of ΔΨm in mitochondria, and inhibited VCSD-induced cytochrome c release from mitochondria as well as cathepsin B from lysosomes. Cathepsin B inhibition (CBI) could also increase cell viability, maintain mitochondrial membrane potential, and repress VCSD-induced release of cytochrome c from mitochondria to cytosol. Both P188 and CBI treatment decreased the cytosolic accumulation of tBid in supernatant of purified lysosomes, and the amount of mitochondrial localized tBid. These data indicate injured neurons have undergone mitochondrial and lysosomal membrane permeability damage, and the mechanism can be exploited with pharmacological interventions. P188's neuroprotection appears to involve a relationship between cathepsin B and tBid-mediated mitochondrial initiation of cell death.

Poloxamer-188 attenuates TBI-induced blood-brain barrier damage leading to decreased brain edema and reduced cellular death.

Plasmalemma permeability plays an important role in the secondary neuronal death induced by traumatic brain injury (TBI). Previous works showed that Poloxamer 188 (P188) could restore the intactness of the plasma membrane and play a cytoprotective action. However, the roles of P188 in blood-brain barrier (BBB) integrity and TBI-induced neural cell death are still not clear. In this study, mice were induced TBI by controlled cortical impact (CCI), and cerebral water content was measured to explore the profile of brain edema after CCI. Further, the regimen of P188 in mouse CCI models was optimized. The neurological test and BBB integrity assessment were performed, and the numbers of TBI-induced neural cell death were counted by propidium iodide (PI) labeling. The expression of apoptotic pathway associated proteins (Bax, cyt-c, caspase-8, caspase-9, caspase-3, P53) and aquaporin-4 (AQP4) was assessed by RT-PCR or immunoblotting. The data showed that the brain edema peaked at 24 h after TBI in untreated animals. Tail intravenous injection of P188 (4 mg/ml, 100 µl) 30 min before TBI or within 30 min after TBI could attenuate TBI-induced brain edema. P188 pre-treatment restored BBB integrity, suppressed TBI-induced neural cell death, and improved neurological function. TBI induced an up-regulation of Bax, cyt-c, caspase-8, caspase-9, caspase-3, and the expression of p53 was down-regulated by P188 pre-treatment. AQP4 mainly located on endothelial cells and astrocytes, and its expression was also regulated by P188 pretreatment. All these results revealed that P188 attenuates TBI-induced brain edema by resealing BBB and regulating AQP4 expression, and suppressed apoptosis through extrinsic or intrinsic pathway. Plasmalemma permeability may be a potential target for TBI treatment.

Necrostatin-1 suppresses autophagy and apoptosis in mice traumatic brain injury model.

Traumatic brain injury (TBI) results in neuronal apoptosis, autophagic cell death and necroptosis. Necroptosis is a newly discovered caspases-independent programmed necrosis pathway which can be triggered by activation of death receptor. Previous works identified that necrostatin-1 (NEC-1), a specific necroptosis inhibitor, could reduce tissue damage and functional impairment through inhibiting of necroptosis process following TBI. However, the role of NEC-1 on apoptosis and autophagy after TBI is still not very clear. In this study, the amount of TBI-induced neural cell deaths were counted by PI labeling method as previously described. The expression of autophagic pathway associated proteins (Beclin-1, LC3-II, and P62) and apoptotic pathway associated proteins (Bcl-2 and caspase-3) were also respectively assessed by immunoblotting. The data showed that mice pretreated with NEC-1 reduced the amount of PI-positive cells from 12 to 48 h after TBI. Immunoblotting results showed that NEC-1 suppressed TBI-induced Beclin-1 and LC3-II activation which maintained p62 at high level. NEC-1 pretreatment also reversed TBI-induced Bcl-2 expression and caspase-3 activation, as well as the ratio of Beclin-1/Bcl-2. Both 3-MA and NEC-1 suppressed TBI-induced caspase-3 activation and LC3-II formation, Z-VAD only inhibited caspase-3 activation but increased LC3-II expression at 24 h post-TBI. All these results revealed that multiple cell death pathways participated in the development of TBI, and NEC-1 inhibited apoptosis and autophagy simultaneously. These coactions may further explain how can NEC-1 reduce TBI-induced tissue damage and functional deficits and reflect the interrelationship among necrosis, apoptosis and autophagy.

[Characteristics and distribution of ERP by different field stimulation].

OBJECTIVE: To study the variation of latency and amplitude of the event related potential (ERP) and its distribution in human scalp when the normal subjects were stimulated with different visual fields. METHODS: The ERP recorded in scalp with the stimulation of 10 degrees visual field and 60 degrees visual field respectively in 20 healthy volunteers with normal visual function. RESULTS: Two different visual field stimulation may evoke the different exogenous components P1 (70-125 ms), N1 (90-170 ms), P2 (140-220 ms) and endogenous components N2 (190-280 ms) and P3 (290-430 ms). The latencies of all the components evoked by 10 degrees visual field were shorter than that of the 60 degrees visual field while the amplitudes of N1 and N2 were lower and appeared over the extensive encephalic region; and the amplitudes of the P1, P2 and P3 were higher and appeared in occipitotemporal, prefrontal and occipital region, respectively. CONCLUSION: Two different visual field stimulation may evoke all the ERP components with significant differences in the latency, amplitude and distribution. The differences may reflect the different visual information integration and processing in human brain during the different visual field stimulation.

Determining the age at death of females in the Chinese Han population: using quantitative variables and statistical analysis from pubic bones.

Determining the age at death of females by skeletal features is extremely difficult and important, both in forensics and in physical anthropology. Our previous study of male pubic symphysis suggests that the indicators of morphological changes provide the best results for personal age identification. The indicators that help deduce of the age of females was approximately the same as males except for two specific indicators, which are bone density of the symphysial surface and viz. Viz are ridges and furrows on the symphysial surface, ossific nodules, lower extremities, ventral and ridge of the rampart, dorsal margin, ventral beveling and general macroscopic changes on the symphysial surface. Samples were drawn from 338 female individuals. The study procedures are as follows: Firstly, we examined the morphological features of pubic symphysis using the criteria similar to Hanihara's, Gilbert-McKern and Suchey-Brooks's methods. Secondly, we evaluated each stage with an appropriate score. Thirdly, we deduced four equations to assess the morphological features of the ages of females by statistic analysis. The results were discussed by comparing with Hanihara's, Gilbert-McKern and Suchey-Brooks's methods. The results were consistent and the developing methods for determining the age of death of females were produced.

[Correlation of pattern reversal visual evoked potentials P100 with visual acuity].

OBJECTIVE: To explore pattern reversal visual evoked potential (PRVEP) P100 components in the patients with different visual acuity and the correlation of P100 components with visual acuity using different visual simulation angles. METHODS: PRVEPs were recorded at Oz point in the patients (100 eyes) with different visual acuity including 0.2, 0.4, 0.6, 0.8 and 1.0 and induced by pattern reversal visual simulation with the different spatial frequencies(check sizes: 8 degrees-7.5'). The latency and amplitude of components P100 were analyzed and statistical analysis was performed using SPSS 13.0 software. RESULTS: The latency and amplitude of P100 wave showed a curvilinear relationship with check sizes. With check size 10 simulation in 0.2 visual acuity group, the P100 latency reached to the minimum and the P100 amplitude showed peak value. Other groups displayed the best value with check size 30'. The P100 latency and amplitude showed a linear correlation with visual acuity. With the increase of visual acuity, the P100 wave latency decreased and the amplitude increased gradually. Regression models between visual acuity and the Pic wave latency and amplitude were also established. CONCLUSION: The regression functions can be an objective and accurate method to evaluate the visual acuity based on the better simulation angles using PRVEP examination.

Cathepsin B contributes to traumatic brain injury-induced cell death through a mitochondria-mediated apoptotic pathway.

It has been reported that lysosomal proteases play important roles in ischemic and excitotoxic neuronal cell death. We have previously reported that cathepsin B expression increased remarkably after traumatic brain injury (TBI). The present study sought to investigate the effects of a selective cathepsin B inhibitor (CBI) [N-L-3-trans-prolcarbamoyloxirane-2-carbonyl)-L-isoleucyl-L-proline] on cell death and behavioral deficits in our model. We examined the levels of cathepsin B enzymatic activity and its expression by double labelling damaged cells in the brain slice with propidium iodide (PI) and anticathepsin B. The results showed an elevated enzymatic activity associated with TBI-induced increase in a mature form of cathepsin B, suggesting that cathepsin B may play a role in TBI-induced cell injury. PI was found to label cells positive for the neuronal-specific nuclear marker NeuN, whereas fewer GFAP-positive cells were labelled by PI, suggesting that neurons are more sensitive to cell death induced by TBI. Additionally, we found that pretreatment with CBI remarkably attenuated TBI-induced cell death, lesion volume, and motor and cognitive dysfunction. To analyze the mechanism of action of cathepsin B in the cell death signaling pathway, we assessed DNA fragmentation by electrophoresis, Bcl-2/Bax protein expression levels, Bid cleavage, cytochrome c release, and caspase-3 activation. The results imply that cathepsin B contributes to TBI-induced cell death through the present programmed cell necrosis and mitochondria-mediated apoptotic pathways.

[The expression and significance of nerve growth factor and its receptors in pancreatic ductal adenocarcinoma].

OBJECTIVE: To investigate nerve growth factor (beta-NGF) and its receptors expression in human pancreatic ductal adenocarcinoma. METHODS: Expression and distribution of beta-NGF, tyrosine kinase A (TrKA) and P75(NGFR) were detected in operation tissue specimens of pancreatic ductal adenocarcinoma with immunohistochemistry and real-time PCR. Relations of beta-NGF and its receptors with clinical pathological characters, especially nerve invasion were analyzed. RESULTS: beta-NGF and TrKA expression are higher in pancreatic adenocarcinoma than normal pancreas, and the differences are significant (P < 0.01). beta-NGF and TrKA expression are associated with the differentiation grades (DG), lymphatic node metastasis, nerve invasion and surgical pathological stages. Poorer of DG and later stages, more expression of beta-NGF and TrKA. beta-NGF and TrKA expression have positive correlations. beta-NGF, TrKA and P75(NGFR) mRNA expression have significantly increased 3.84, 4.23 and 2.41 times than normal tissues by real-time PCR, respectively. CONCLUSIONS: beta-NGF and TrKA might play potential roles in carcinogenesis for pancreatic cancer, have affinity with clinicopathological characters of pancreatic cancer. beta-NGF and TrKA may have mutual effect in signal transduction leading to perineural invasion of pancreatic carcinoma.

[The progress in the study of visual field in spatial attention by event related potentials].

Event-related potentials (ERP) is a good temporal resolution method to study the mechanism of visual field in brain. With the development of technique of high-density recording and brain imaging, the ERP is widely used in the location of the brain function. This article reviews the methods, results and primary conclusions in the field, and suggests several perspectives for the future research and application of ERP in the forensic science.