Application of Sequential Changes of Dural Thickness and Biomechanical Parameters in Postmortem Interval Estimation / 法医学杂志

Objective To study the relations of the dural thickness and the biomechanical parameters with postmortem interval （PMI） of human cadavers, and to explore the feasibility of the two indexes used for PMI estimation. Methods Dural samples were collected at different postmortem intervals of 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 48 h, 60 h, 72 h, 84 h and 96 h, then fabricated into 4.0 cm×1.0 cm A and B test specimens. The thickness of the A test specimen was measured, and the biomechanical parameters, such as ultimate load, maximum force deformation, tensile strength, elastic modulus and fracture force, were measured. The regression equations of thickness, biomechanical parameters and PMI were fitted respectively, and the difference between the predicted value and actual measured value of PMI was verified by the verification group. The B test specimen was fixed with 10% neutral formaldehyde solution, then tissue sections were prepared to observe its morphological changes. Results From 6 h to 96 h after death, the dural thickness decreased gradually, the collagen fibers gradually changed from clear arrangement to mutual fusion, and the number of nuclei decreased gradually. The dural thickness, ultimate load, tensile strength, elastic modulus and fracture force decreased sequentially, among which the dural thickness, ultimate load, elastic modulus and fracture force had a correlation with PMI （P<0.05）. In the return test, the difference between the predicted value and actual measured value of PMI in the verification group had no statistical significance （P>0.05）. Conclusion The dural thickness, ultimate load, elastic modulus and fracture force change sequentially from 6 h to 96 h after death. The regression equation established by the relationship between the changes and PMI can be used for PMI estimation.

Effects of activation or blockade of 5-HT1A receptors in the medial septum-diagonal band of Broca complex on cognitive functions in hemiparkinsonian rats / 西安交通大学学报(医学版)

Objective To explore the role and mechanisms of 5-HT1Areceptors in the medial septum-diagonal band of Broca complex (MS-DB) in hemiparkinsonian rats. Methods Combined behavioral and electrophysiological studies were performed to assess the role of MS-DB 5-HT1Areceptors in working memory and hippocampal theta rhythm in rats with 6-hydroxydopamine (6-OHDA)lesions in the medial forebrain bundle (MFB).Results ① MFB lesions in the rats decreased choice accuracy in the T-maze rewarded alternation test. Intra-MS-DB injection of 5-HT1Areceptor agonist 8-OH-DPAT further decreased choice accuracy,while intra-MS-DB injection of 5-HT1Areceptor antagonist WAY-100635 increased choice accuracy in the lesioned rats.② MFB lesions in the rats decreased peak theta rhythm frequency. Intra-MS-DB injection of 8-OH-DPAT suppressed hippocampal theta rhythm and decreased normalized theta power,while intra-MS-DB injection of WAY-100635 induced theta rhythm and increased normalized theta power.Conclusion Blockade of MS-DB 5-HT1Areceptors can recover cognitive dysfunction in Parkinson's disease, which may be attributed to the enhancement of hippocampal theta rhythm.

Firing activity of locus coeruleus noradrenergic neurons increases in a rodent model of Parkinsonism / 神经科学通报·英文版

<p><b>OBJECTIVE</b>To investigate the changes in the firing activity of noradrenergic neurons in the locus coeruleus (LC) in a rat model of Parkinson disease (PD).</p><p><b>METHODS</b>2 and 4 weeks after unilateral lesion of the nigrostriatal pathway in the rat by local injection of 6-hydroxydopamine (6-OHDA) into the right substantia nigra pars compacta (SNc), the firing activity of noradrenergic neurons in LC was recorded by extracellular single unit recording.</p><p><b>RESULTS</b>The firing rate of LC noradrenergic neurons increased significantly 2 and 4 weeks after 6-OHDA lesions compared to normal rats, respectively (P < 0.05). The percentage of irregularly firing neurons was obviously higher than that of normal rats during the fourth week after SNc lesion (P < 0.05).</p><p><b>CONCLUSION</b>LC noradrenergic neurons are overactive and more irregular in 6-OHDA-lesioned rats. These changes suggest an implication of the LC in the pathophysiological mechanism of PD.</p>

The selective 5-HT(1A) receptor antagonist WAY-100635 increases neuronal activity of the basolateral nucleus of the amygdala in 6-hydroxydopamine-lesioned rats / 生理学报

In the present study, extracellular recording was used to examine the neuronal activity of the basolateral nucleus (BL) of the amygdala and the effects of systemic administration of the selective 5-HT(1A) receptor antagonist WAY-100635 on the neuronal activity in the normal rats and rats with 6-hydroxydopamine (6-OHDA)-produced lesions in the substantia nigra pars compacta (SNc). The results showed that the firing rates of BL projection neurons and interneurons were (0.39±0.04) Hz and (0.83±0.16) Hz in the normal rats, and (0.32±0.04) Hz and (0.53±0.12) Hz in 6-OHDA-lesioned rats. There was no significant difference in the firing rates of BL projection neurons and interneurons between the normal and 6-OHDA-lesioned rats. In the normal rats, all BL projection neurons fired in burst; 94% of BL interneurons fired in burst and 6% fired irregularly. In 6-OHDA-lesioned rats, 85% of BL projection neurons displayed a burst firing pattern and 15% fired irregularly; 86% of BL interneurons had a burst firing pattern and 14% fired irregularly. The distribution of firing patterns of projection neurons and interneurons in the BL in 6-OHDA-lesioned rats did not differ from that in the normal rats. Systemic administration of WAY-100635 at 0.1 mg/kg body weight did not change the mean firing rates of projection neurons and interneurons in the BL in both normal and 6-OHDA-lesioned rats. However, a higher dose of WAY-100635 at 0.5 mg/kg body weight significantly decreased the mean firing rate of BL projection neurons from (0.43±0.07) to (0.15±0.02) Hz in the normal rats (P<0.01), but significantly increased the activity of BL projection neurons in 6-OHDA-lesioned rats from (0.37±0.08) to (0.69±0.18) Hz (P<0.004). The mean firing rates of BL interneurons in the normal and 6-OHDA-lesioned rats did not change after administration of a higher dose of WAY-100635 at 0.5 mg/kg body weight. These results demonstrate that the activity of BL neurons after substantia nigra dopaminergic lesion in the SNc is regulated by activation of intrinsic and extrinsic inputs, and that 5-HT(1A) receptors significantly contribute to the regulation of the activity of BL projection neurons in both normal and 6-OHDA-lesioned rats. Furthermore, WAY-100635 induced an increase in the mean firing rate of projection neurons in the BL in 6-OHDA-lesioned rats, suggesting that 5-HT(1A) receptor is likely to play a role in generating affective symptoms in Parkinson's disease.

The selective 5-HT1A receptor antagonist WAY-100635 inhibits neuronal activity of the ventromedial prefrontal cortex in a rodent model of Parkinson's disease / 神经科学通报·英文版

<p><b>OBJECTIVE</b>The ventral part of the medial prefrontal cortex (mPFC) plays an important role in initiation and control of voluntary movement, mood and cognition. However, after the degeneration of the nigrostriatal pathway, the neuronal activity of the ventral mPFC and the role of serotonin(1A) (5-hydroxytryptamine, 5-HT(1A)) receptors in the firing of the neurons are still unknown. The present study is to investigate the change of neuronal activity in the ventral mPFC and the effect of systemic administration of the selective 5-HT(1A) receptor antagonist WAY-100635 on the activity of the neurons in normal and 6-hydroxydopamine (6-OHDA)-lesioned rats.</p><p><b>METHODS</b>Single unit responses were recorded extracellularly with glass microelectrodes from ventral mPFC neurons in normal rats and 6-OHDA unilaterally lesioned rats in vivo.</p><p><b>RESULTS</b>6-OHDA lesion of the substantia nigra pars compacta (SNc) significantly increased the firing rate with no change in the firing pattern of neurons of the ventral mPFC in rats. Systemic administration of WAY-100635 (0.1 mg/kg, i.v.) did not change the mean firing rate and firing pattern of ventral mPFC neurons in normal rats. In contrast, WAY-100635 significantly decreased the mean firing rate of the neurons in rats with 6-OHDA lesion of the SNc.</p><p><b>CONCLUSION</b>These data suggest that the degeneration of the nigrostriatal pathway results in an increase of neuronal activity of ventral mPFC and dysfunction of 5-HT(1A) receptor.</p>

Changes in the firing activity of serotonergic neurons in the dorsal raphe nucleus in a rat model of Parkinson's disease / 生理学报

In the present study, changes in the neuronal activity of serotonergic neurons in the dorsal raphe nucleus (DRN) and the effect of the selective 5-HT(1A) receptor antagonist WAY-100635 in a rat model of Parkinson's disease (PD) were investigated by using extracellular single unit recording. Rat model of PD was produced by microinjection of 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta on the right side of the brain. The results showed that the mean spontaneous firing rate of DRN serotonergic neurons in the control and 6-OHDA-lesioned rats were (1.76+/-0.11) spikes/s (n=24) and (2.43+/-0.17) spikes/s (n=21), respectively. The firing rate of serotonergic neurons in 6-OHDA-lesioned rats was significantly higher than that in the control rats (P<0.001). In the control rats, 92% (22/24) of the neurons fired regularly and 8% (2/24) fired in bursts. In rats with 6-OHDA lesions, 9% (2/21) of neurons fired regularly, 43% (9/21) exhibited irregular pattern and 48% (10/21) fired in bursts. The percentage of DRN serotonergic neurons firing in bursts was obviously higher in 6-OHDA-lesioned rats than that in the control rats (P<0.001). Local injection of WAY-100635 (3 microg in 200 nL) into the DRN significantly increased the firing rate of serotonergic neurons with no change in firing pattern in the control rats (n=19, P<0.002), but did not change the firing rate and firing pattern of serotonergic neurons in 6-OHDA-lesioned rats (n=17, P>0.05). These results suggest the dysfunction of 5-HT(1A) receptor in 6-OHDA-lesioned rats and the involvement of the DRN in the pathophysiological mechanism of PD.

Increased subthalamic neuronal activity after dorsal raphe nucleus lesion by 5,7-dihydroxytryptamine in the rat / 生理学报

In vivo extracellular recordings were made in the subthalamic nucleus (STN) of intact control rats and rats with 5,7-dihydroxytryptamine (5,7-DHT) -produced lesion of dorsal raphe nucleus (DRN). The results showed that the firing rate of STN neurons in control rats and DRN-lesioned rats were (6.93+/-6.55) Hz and (11.27+/-9.31) Hz, respectively, and the firing rate of DRN-lesioned rats significantly increased when compared to the control rats (P<0.01). In control rats, 13% of STN neurons discharged regularly, 46% irregularly and 41% in bursts. In DRN-lesioned rats, 9% of STN neurons discharged regularly, 14% irregularly and 77% in bursts, the percentage of STN neurons firing in bursts was obviously higher than that of the control rats (P<0.01). In addition, the mean interspike interval coefficient of variation of STN neurons in control rats and DRN-lesioned rats were (0.05+/-0.04) and (0.11+/-0.09), respectively. The mean interspike interval coefficient of variation of DRN-lesioned rats was significantly higher than that of the control rats (P<0.001). These results show that the firing rate and the bursting pattern rate of neurons in STN of DRN-lesioned rats increase significantly, suggesting that DRN inhibits the neuronal activity of the subthalamic neurons in the intact rat.

Changes of discharge rate and pattern of 5-hydroxytrypamine neurons of dorsal raphe nucleus in a rat model of Parkinson's disease / 生理学报

In the present study, changes of the neuronal activity of 5-hydroxytrypamine (5-HT) neurons of dorsal raphe nucleus(DRN) in a rat model of Parkinson's disease (PD) were investigated with glass microelectrode recording. The results showed that the discharge rates of 5-HT neurons in control and PD rats were (1.61+/-0.56) Hz and (2.61+/-1.97) Hz, respectively. The discharge rate of PD rats was significantly increased when compared to that of the control rats. In control rats, 79% of 5-HT neurons discharged regularly and 21% in bursts. In PD rats, however, 36% of 5-HT neurons discharged regularly, 16% irregularly and 47% in bursts. The percentage of 5-HT neurons discharging in bursts was obviously higher than that of the control rats (P<0.05). The data suggest that the discharge rate and bursting pattern of 5-HT neurons in DRN are increased in a rat model of Parkinson's disease.

Prostaglandin inhibitor indomethacin inhibits afferent activities of Adelta and C units in the saphenous nerve of diabetic hyperalgesic rats / 生理学报

The effects of a non-selective inhibitor of cyclo-oxygenase (COX) indomethacin, and exogenous prostaglandin E(2) (PGE(2)) on A(delta) units and C units in the saphenous nerve of diabetic hyperalgesic rats were studied. The results showed that the conduction velocity of A(delta) units and C units and their mechanical threshold in diabetic hyperalgesic rats were obviously decreased, and a small number of A(delta) units (4/24) and C units (2/18) produced increased spontaneous activities. Intraperitoneal injection of indomethacin in diabetic hyperalgesic rats significantly relieved mechanical hyperalgesia, and resulted in a decrease in spontaneous afferent activities of the A(delta) units and C units. Subcutaneous injection of exogenous PGE(2) into the diabetic hyperalgesic and control rats produced a significant decrease in mechanical threshold of the A(delta) units and C units, and elicited discharge from 3 A(delta) units (3/24) and 1 C unit (1/18) in diabetic hyperalgesic rats and from 2 A(delta) units (2/13) in control rats. The present data suggest that the synthesis and release of PGs are increased in diabetic neuropathy, PGs can sensitize and /or activate A(delta) units and C units and elicit hyperalgesia and allodynia in diabetic rats.