Effects of Different Crystalloid Fluids on Renal Tissue in an Experimental Model of Hemorrhagic Shock.

Objective: The type of fluid that should be used in uncontrollable hemorrhages remains an area of research. This study was designed to compare the effects of resuscitation with Ringer's lactate (RL) solution versus a normal saline (NS) solution on hemodynamics, renal tissue histopathology, coagulation, and apoptosis in a rat model of hemorrhagic shock. Methods: The study employed groups designated as the control, hemorrhage, NS, and RL groups. Heart rate, mean arterial pressure, and respiratory rate were monitored. Annexin A5 values were assayed, rotational thromboelastometry analysis was performed, and excised kidney tissue samples were histopathologically analyzed. Results: Blood pressure levels were found to be significantly higher in the control group than those measured in the other groups. While the clotting time (CT) and clot formation time (CFT) in the hemorrhage group were significantly longer than those in the control and RL groups, the CT and CFT measured in the control group were significantly shorter compared to the RL group. The mean Annexin A5 level was in the hemorrhage group, which was significantly higher compared to the other groups. In the renal histopathological evaluation, the scores of proximal tubular injury, distal renal tubular injury, and interstitial renal tubular injury were found to be significantly lower in the control group compared to the other groups. Conclusion: This study demonstrated that NS or RL can be used safely to improve the hemodynamic symptoms resulting from hemorrhagic shock as a means to reduce apoptosis, and to decrease findings in favor of coagulopathy in bedside coagulation tests during the early stages of hemorrhagic shock until the time of starting a blood transfusion.

Investigating the mechanism of action of ginkgolides and bilobalide on absence seizures in male WAG/Rij rats.

The effects of a single and multiple doses of ginkgolide A, B, C, and bilobalide, active components of Ginkgo biloba extract (EGb 761), on absence seizures were investigated in male WAG/Rij rats, a genetic animal model of absence epilepsy. Furthermore, the interactions of ginkgolide A together with NMDA receptor antagonist MK-801, AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), or L-type calcium channel blocker nicardipine were studied to figure out how ginkgolide A affects spike-wave discharges (SWDs) in the brain. The experiments were done using 6-8-month-old male WAG/Rij rats with infusion cannula and EEG electrode implanted. Ginkgolide A, B, C, and bilobalide were administered intraperitoneally for 7 days at a dose of 6 mg/kg. In interaction groups, 6 µg ginkgolide A was injected intracerebroventricularly in combination with MK-801 (10 µg), CNQX (1 µg), and nicardipine (50 µg) for 7 days. EEG was recorded from animals at the baseline, first dose, and seventh dose periods for 4 h. Ginkgolide A (p = .028), C (p = .046), and bilobalide (p = .043) significantly increased the frequency of SWDs in WAG/Rij rats. Ginkgolide A injected into the lateral ventricle with MK-801 (p = .046), CNQX (p = .043), and nicardipine (p = .046) significantly increased the number of SWDs after seventh dose. Finally, the EGb 761-related increase in absence epilepsy was determined to be caused by ginkgolide A, C, and bilobalide. All three receptor antagonists/channel blockers do not inhibit the pro-absence effect of ginkgolide A. The findings revealed that ginkgolide A's pro-absence effect is mediated by brain circuits other than ionotropic glutamate receptors or L-type calcium channels.

The effects of hydroxyethyl starch and gelatine on lung tissue and coagulation during the resuscitation of rats with traumatic haemorrhagic shock.

INTRODUCTION: This study was constructed to compare the effects of resuscitation with gelatine and hydroxyethyl starch (HES) on coagulopathy, haemodynamics, and tissue damage during an uncontrolled haemorrhagic shock model in rats. MATERIAL AND METHODS: Twenty 6-month-old Sprague-Dawley rats were included in the study and divided into 4 groups. There was no haemorrhage in the sham group. The others were randomised into haemorrhage without volume replacement (control group), haemorrhage and gelatine (group G), and haemorrhage and HES (group V). Blood samples for thromboelastogram and annexin 5 values were obtained before bleeding and after resuscitation. RESULTS: In the control group, R (16.18 ± 2.74) and K (5.8 ± 1.1) were significantly higher than in all other groups ( P = 0.001), and the TEG alpha angle was 39.54 ± 5.94°, which was found to be significantly lower than in the sham group ( P = 0.001). In group V, the TEG MA value was found to be significantly lower at 30.54 ± 8.89 ( P = 0.001). The annexin A5 value was significantly higher in the control group, group V, and group G than in the sham group and was highest in the control group ( P = 0.001). Lung damage score measurement was 0.60 ± 0.19 in the control group, higher than in the gelatine and HES groups ( P = 0.001). CONCLUSIONS: Lung tissue damage and coagulation were positively affected by HES or gelatine resuscitation. A reduction in clot formation in the HES group might be observed due to the possible negative effect on platelets. Therefore, we concluded that the use of gelatine might be advantageous until blood transfusion is initiated in traumatic haemorrhagic shock.

Electroencephalographic investigation of the effects of Ginkgo biloba on spike-wave discharges in rats with genetic absence epilepsy.

OBJECTIVE: EGb 761, a plant extract obtained from the leaves of the Ginkgo biloba tree, is widely used in modern medicine and traditional medicine applications in the treatment of many diseases. However, in some clinical case reports, it has been suggested that G. biloba causes epileptic seizures. A limited number of experimental animal studies related to the effects of G. biloba on epileptic seizures do not provide sufficient information on the solution of a serious clinical problem with contrasting findings. We aimed to investigate the effects of EGb 761 administered in different doses to adult male Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats which is the genetic animal model of absence epilepsy, on absence seizures using in vivo electrophysiological method. In addition, the effects of EGb 761 doses on locomotor behavior of WAG/Rij rats were evaluated with open-field and rotarod behavioral tests. METHODS: 50, 100, 200, and 400 mg/kg doses of EGb 761 were administered to male WAG/Rij rats with implanted EEG electrodes by oral gavage for 28 days. Evaluation of absence seizures was performed on spike-wave discharges (SWDs) in EEG recorded for 4 h each week. The number of SWDs, the total duration of SWDs, and the mean duration of SWD were determined for the analysis. RESULTS: In the group treated with 400 mg/kg EGb 761, the number of SWDs and the mean duration of SWD at the 1st and 7th doses and the total duration of SWDs at the 1st, 7th and 14th doses were significantly increased (p < 0.05). In all experimental groups treated with EGb 761 doses, there was no significant change in locomotor activity in the open-field and the rotarod tests. CONCLUSION: Ginkgo biloba extract EGb 761 increased the epileptic SWD parameters of WAG/Rij rats at high doses (400 mg/kg), causing a pro-epileptic effect on absence seizures. It should be noted that in patients with epilepsy and in high-dose applications, G. biloba extract EGb 761 may lead to an increase in neuronal excitability.

Combination Therapy of Gabapentin and N-Acetylcysteine Against Posttraumatic Epilepsy in Rats.

Traumatic brain injury (TBI) is a major public health problem worldwide that is associated with increased mortality and morbidity. Posttraumatic epilepsy (PTE) is one of the sequelae of TBI. The aim of this study was to investigate the role of N-acetylcysteine (NAC) as an adjuvant on the efficacy of levetiracetam (LEV) and gabapentin (GBP) in PTE model encouraged by pentylenetetrazol (PTZ) after mild-TBI in male Sprague-Dawley rats. Mild-TBI was performed by the weight-drop method in male Sprague-Dawley rats. PTE model was developed by injecting PTZ (30+15+15 mg/kg, 30 min intervals, i.p.) 7 days after head trauma. After the development of posttraumatic seizures, the rats were treated with NAC (100 mg/kg), LEV (50 mg/kg), GBP (100 mg/kg), NAC+LEV and NAC+GBP intraperitoneally for 14 days. Seizures related to PTE were scored by video-EEG recording. Motor performance of the animals was also evaluated in the rotarod test. 50 mg/kg LEV and 100 mg/kg GBP reduced seizures related to PTE. LEV alone (p = 0.009), but the administration of GBP+NAC (p = 0.015) was more effective on PTE-related seizure control. However, GBP+NAC application adversely affected the fall latency in the rotarod test. In terms of trauma-related seizure control, there was no statistically significant difference between the use of prophylactic LEV and symptomatic LEV. LEV alone or the combination of GBP with NAC provides more effective seizure control in the PTE facilitated by PTZ. On the other hand, the use of prophylactic LEV did not have any extra effect on posttraumatic seizure development and control.

Ischemia-modified albumin and the IMA/albumin ratio in the diagnosis and staging of hemorrhagic shock: A randomized controlled experimental study.

BACKGROUND: To determine the value of ischemia-modified albumin (IMA) and IMA/albumin ratio (IMAR) in the diagnosis and staging of hemorrhagic shock (HS). METHODS: A pressure-targeted HS model was established in this study. The control and shock groups were monitored for 30 min and 60 min to simulate varying durations of exposure to HS. All subjects underwent invasive arterial monitoring during the experiment and were further divided into mild and severe shock groups based on decreases in mean arterial pressure (MAP). Biochemical and histologic comparisons were performed between the groups. RESULTS: Our results revealed higher IMA, IMAR, lactate, total oxidant status (TOS) and oxidative stress index (OSI) levels in both the 30- and 60-min shock groups compared to the control group. Concerning MAP-based shock staging, IMA, IMAR, lactate, TOS and OSI levels in the 30-min and 60-min mild and severe shock groups were higher than those of the controls. However, there was no significant difference between the mild and severe shock groups. A significant correlation was determined between all the biomarkers evaluated and HS-induced damage in various organs. This correlation was highest in lactate and IMAR levels. CONCLUSION: IMA and IMAR levels may be used in the early diagnosis of HS and also have the potential for use in determining the severity of HS. IMA and IMAR measurement may also be considered as an alternative or in addition to lactate measurement in the diagnosis of HS.

Electrophysiological evidence on epileptiform activity enhanced by electrical stimulation of teeth in rats.

The aim of this study was to evaluate the possible effects of electrical stimulation (ES) of tooth on penicillin-induced epileptiform activity in rats. Experiment was realized on 24 adult male Sprague Dawley rats. Rats were assigned three groups [stimulation group (SG), penicillin group (PG), and penicillin+stimulation group (PSG)]. In SG, ES was only applied. Ten pulses of electrical current were delivered to the teeth for a duration of 2 milliseconds at 1-second intervals from a stimulator. Currents were applied in the range of 40-240 µA with 40 µA steps. Electrocorticography (ECoG) recordings were taken before and after ES. In PG, ECoG recordings were taken before and during the injection of penicillin. In PSG, after epileptiform activity was induced, ES was applied and ECoG recordings were taken as in SG. All the data were analyzed with Student's t test. Applied currents did not cause any epileptiform activity in SG. When the PSG was compared with the PG it was seen that the spike frequency of epileptiform activity increased in a statistically significant way after application of 240 µA (P < 0·05). On the other hand current application caused an increase in the spike amplitude of the PSG compared with the amplitude of the PG, but it was not statistically significant. We concluded that ES of tooth with high current can trigger epileptiform activity in rats. For this reason, further research is required to evaluate the effects of ES of tooth for pulp testing on epileptic human subjects and antiepileptic drug users.

Efficacy of dexamethasone on penicillin-induced epileptiform activity in rats: an electrophysiological study.

Corticosteroids are extensively used in treatment of many diseases. In neurosurgery practice, dexamethasone (DEX) is commonly used particularly in cerebral edema secondary to brain tumors, head trauma, and central nervous system infections. There are some uncertainties surrounding the secure use of DEX in patients with epilepsy or seizures induced by diseases of the central nervous system such as head trauma and brain tumors. Despite its extensive use, the effect of DEX on epileptiform activity is unclear. In this study the effect of DEX on epileptiform activity was investigated in rats. The effects of 1, 3, and 10mg/kg DEX on epileptiform activity was compared with effects of antiepileptic drugs commonly employed in treatment of epilepsy, namely phenytoin (PHT) 50mg/kg and levetiracetam (LEV) 50mg/kg that were administered intraperitoneally for 1 week. All groups were administered intracortical penicillin (500IU) to induce epileptiform activity. DEX at the doses of 3mg/kg and 10mg/kg significantly reduced spike frequencies compared to the initial values. In conclusion, we think that DEX can effectively decrease the epileptiform activity.

Evaluation of the role of chronic daily melatonin administration and pinealectomy on penicillin-induced focal epileptiform activity and spectral analysis of ECoG in rats: an in vivo electrophysiological study.

In the present study, we aimed to investigate the effects of pinealectomy and chronic melatonin administration on focal epileptiform activity induced by penicillin in the rat cortex and to determine the relation between melatonin levels and electrocorticogram (ECoG) power spectrum. For this purpose, male Sprague-Dawley rats were divided into six groups: control, sham operated, ethanol, melatonin, pinealectomy and pinealectomy + melatonin group. Melatonin-treated rats was intraperitoneally injected with a daily single dose of 10 mg/kg melatonin for 14 days, but the last dose was given 30 min after local application of penicillin as a convulsant agent. Focal epileptiform activity was produced by intracortical administration of penicillin (200 units/1 µl). While chronic melatonin application did not affect either the onset latency or the spike frequency of epileptiform activity, pinealectomy significantly reduced latency to onset of initial epileptiform discharges and increased cortical epileptiform activity. However, acute melatonin administration decreased the epileptiform activity. The results also indicated that exogenously applied melatonin did not change the spectral analysis of ECoG, but pinealectomy led to a reduction in the power of the fast bands (gamma) power in ECoG. We conclude that endogenous melatonin signaling seem to have a tonic inhibitory action on neuronal excitability and epileptiform activity, and also a certain concentration of melatonin required for normal cortical excitability.

Electrophysiological evidence for the anticonvulsant effect of alpha-lipoic acid via indirect antioxidant properties in BALB/c mice.

Alpha-lipoic acid (alpha-LA) is a strong antioxidant whose effect on epilepsy has not been completely clarified yet. The present study was designed to investigate the effects of alpha-LA on epileptiform activity induced by penicillin in BALB/c mice. In the present study, 56 adult male BALB/c mice were divided into seven groups. Under urethane anesthesia, the mice were injected with intracortical (i.c.) 200 IU penicillin following craniotomy to start epileptiform activity. The effects of alpha-LA on epileptiform activity were examined through the intraperitoneal (i.p.) application of 25, 50, 100, 200, and 400 mg/kg doses. The electrophysiological data have demonstrated that alpha-LA at the 200 mg/kg dose showed an anticonvulsant effect by reducing penicillin-induced epileptiform activity. This effect obtained at the 200 mg/kg dose was determined to emerge 80 minutes after injection (i.p.) and last throughout the experiment. Alpha-LA (400 mg/kg) was appointed as the toxic dose for the BALB/c mice used in this study. The findings of the study indicate that alpha-LA at the 200 mg/kg dose show an anticonvulsant effect by reducing penicillin-induced epileptiform activity. Besides this, the delayed anticonvulsant effect of alpha-LA observed in this study gives the impression that it could result from its indirect antioxidant activity.

Comparison of focally induced epileptiform activities in C57BL/6 and BALB/c mice by using in vivo EEG recording.

Epilepsy characterized by repeated seizures is influenced by genetic factors. Seizure response of inbred mouse strains changes depending on the variety of stimuli including chemical (e.g., pentylenetetrazole, nicotine, cocaine, NMDA, kainate), physical (e.g., auditory) or electrical. In this study, we compared the susceptibilities of C57BL/6 and BALB/c mice strains to penicillin induced epileptiform activity (a focally induced, experimental epilepsy model), by analyzing the spike onset latency, spike amplitude and spike frequency. The power spectrums of baseline EEGs were also investigated. We found no alterations of spike onset latencies between the C57 and BALB mice. However, spike amplitudes and spike frequencies were found to be higher in BALB mice than C57 mice. With regard to EEG power spectrum, absolute power of investigated bands was not different between the two strains. Interestingly, the relative power of all investigated bands differed significantly between two strains. The relative power of delta and theta was lower whereas relative power of alpha, beta and gamma was higher in C57 mice compared to BALB mice. In conclusion, our findings showed that BALB mice are more sensitive to penicillin induced epileptiform activity when compared to C57 strain.

Penicillin induced epileptiform activity and EEG spectrum analysis of BDNF heterozygous mice: an in vivo electrophysiological study.

Brain-derived neurotrophic factor (BDNF) heterozygous mice (BDNF (+/-)) kindle slowly and have a higher seizure threshold. However, BDNF (+/-) mice exhibit reduced cortical inhibition and disrupted balance of excitation/inhibition synaptic transmission. We investigated penicillin-induced focal cortical epileptiform activity and electroencephalogram (EEG) spectral power of BDNF (+/-) mice, by using electrocorticogram (ECoG) recordings. BDNF (+/-) mice (n=10) and wild type littermates (n=9) were anesthetized with i.p. urethane (1.750g/kg). The recordings of ECoG were carried out by using a data acquisition system and 100IU penicillin was administered intracortically to induce epileptiform activity. The latencies for the onset of spikes and the amplitude of the spikes showed no differences. However the frequency of the spikes was significantly lower in BDNF (+/-) mice at 40th and 45th min following penicillin injection. Additionally, the EEG power for both BDNF (+/-) and wild type mice reduced after penicillin injection and enhanced during epileptiform activity. The spectral power analysis also revealed that the absolute Gamma power of BDNF (+/-) was significantly smaller than wild types. The results of the present study provide the first in vivo electrophysiological evidence that BDNF heterozygous mice exhibited suppressed epileptiform activity. Moreover, reduced levels of BDNF led to a reduction of absolute Gamma band power.