Rabbit Brain Research Articles

Application of 3.0T susceptibility weighted imaging in the diagnosis of hemorrhagic foci and the outcome prediction of rabbits with brain blast injury

To investigate the value of susceptibility weighted imaging(SWI)in the diagnosis of hemorrhagic foci early after blast injury and its role in the outcome prediction. Totally 30 rabbits with blast-induced cerebral blast injury were used in this study. After routine CT/MRI and SWI scanning,quantified analysis was performed in regions of interest using post-processing technology. After dissecting the brains of the experimental rabbits,the cerebral histopathological changes were observed,and the results were compared with SWI findings. In these 30 rabbits,22,102,221,and 738 hemorrhagic foci were detected by CT,T1WI,T2WI,and SWI,respectively. The number of cerebral microbleeds detected by SWI was significantly larger than those revealed by conventional T1WI and T2WI(Χ(2)=10.00,P<0.01). Furthermore,the SWI imaging displayed the punctiform(n=315,42.7%),lamellar(n=218,29.5%),slinar(n=205,27.8%)hypointense foci,with clear margin. The number of hemorrhagic foci detected by SWI was positively correlated with survival(r=-0.667,P<0.05). SWI remarkably increases the detection rate of hemorrhagic foci(particularly microbleeds)in rabbits with cerebral blast injury. The number of cerebral microbleeds and location of foci are closely related with the outcomes and therefore may facilitate clinical managment.

Leptin’s effect on accelerated fracture healing after traumatic brain injury

Objective: To investigate mechanisms behind the faster rehabilitation of limb fractures when associated with traumatic brain injury (TBI).Methods: New Zealand rabbits were divided into TBI group and sham-operation group for four studies as follows: (1) blood and cerebrospinal fluid (CSF) were drawn on days 1, 3, and 7 to demonstrate changes in serum leptin, growth hormone (GH), insulin-like growth factor 1 (IGF-1), and CSF leptin; (2) bone defection was created by drilling in the tibial bone and either leptin or normal saline was injected into rabbit’s cerebellomedullary cistern. X-ray was taken at 1 days, 2 weeks, and 5 weeks and evaluated by criteria to determine rate of bone healing; (3) FITC-labeled rabbit leptin was injected into TBI and sham-operation groups, and frozen sections of rabbit brain were observed to identify differences in central nervous system (CNS) leptin by fluorescence; (4) polymerase chain reaction (PCR) was used to evaluate the expression of leptin production by brain tissue.Results: Serum and CSF leptin, GH, and IGF-1 concentrations were found to be higher in the TBI group than the sham-operation group at days 1, 3, and 7 (P<0·05). CSF leptin of the TBI group was positively correlated with serum leptin on day 1 (P<0·05), and positively correlated with GH and IGF-1 on days 3 and 7 (P<0·05). X-ray criteria demonstrated that leptin administration caused significantly faster healing calluses at 3 and 5 weeks as compared to control animals (P<0·05). FITC-labeled leptin study demonstrated that TBI animals had stronger expression of leptin in the brain than sham-operated animals. However, PCR of brain tissue leptin showed no significant differences between TBI and sham-operated animals in the expression of leptin.Conclusions: Our study suggests that increased CSF leptin, likely from blood–brain barrier breakdown, combined with elevated serum GH and IGF-1 after TBI, leads to accelerated fracture healing.

Metabolomics Reveals Metabolic Alterations by Intrauterine Growth Restriction in the Fetal Rabbit Brain

BackgroundIntrauterine Growth Restriction (IUGR) due to placental insufficiency occurs in 5–10% of pregnancies and is a major risk factor for abnormal neurodevelopment. The perinatal diagnosis of IUGR related abnormal neurodevelopment represents a major challenge in fetal medicine. The development of clinical biomarkers is considered a promising approach, but requires the identification of biochemical/molecular alterations by IUGR in the fetal brain. This targeted metabolomics study in a rabbit IUGR model aimed to obtain mechanistic insight into the effects of IUGR on the fetal brain and identify metabolite candidates for biomarker development.Methodology/Principal FindingsAt gestation day 25, IUGR was induced in two New Zealand rabbits by 40–50% uteroplacental vessel ligation in one horn and the contralateral horn was used as control. At day 30, fetuses were delivered by Cesarian section, weighed and brains collected for metabolomics analysis. Results showed that IUGR fetuses had a significantly lower birth and brain weight compared to controls. Metabolomics analysis using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and database matching identified 78 metabolites. Comparison of metabolite intensities using a t-test demonstrated that 18 metabolites were significantly different between control and IUGR brain tissue, including neurotransmitters/peptides, amino acids, fatty acids, energy metabolism intermediates and oxidative stress metabolites. Principle component and hierarchical cluster analysis showed cluster formations that clearly separated control from IUGR brain tissue samples, revealing the potential to develop predictive biomarkers. Moreover birth weight and metabolite intensity correlations indicated that the extent of alterations was dependent on the severity of IUGR.ConclusionsIUGR leads to metabolic alterations in the fetal rabbit brain, involving neuronal viability, energy metabolism, amino acid levels, fatty acid profiles and oxidative stress mechanisms. Overall findings identified aspargine, ornithine, N-acetylaspartylglutamic acid, N-acetylaspartate and palmitoleic acid as potential metabolite candidates to develop clinical biomarkers for the perinatal diagnosis of IUGR related abnormal neurodevelopment.

The effect of hypotension on rabbit brain injury induced by carotid stenosis

Objective To observe the changes of neuron-specific enolase (NSE)and S100β concentration in plasma of the bilateral carotid moderate stenosis rabbits following hypotension induced by different interventions,and to explore the injury effect of perioperative hypotension on carotid stenosis rabbit brain.Methods Choose the adult rabbit to establish bilateral carotid moderate stenosis rabbit model.The rabbits were randomly divided into four groups.in addition to the control group,the other three groups rabbits all decreased blood pressure by 20％-30％ induced by bloodletting,nitroglycerin and propofol,and maintain for 20 min,than restore blood pressure,Took blood samples,after blood pressure restoration 7.5,24 h respectively and measured NSE and S100β protein in serum,then compared with the extent of brain damage.Results Compared with the blood samples of the control group,NSE and S100β values in each observation time point all increased in three hypotension groups,and there wree significant difference (P＜0.05).NSE and S 100β values were (1 486.51 ±19.22) μg/L and (592.13 ± 10.09) μg/L respectively in propofol group after decreasing blood pressure 7.5 h,NSE protein expression index increased a little than the bloodletting group,nitroglycerin group at each time point,There were significant difference among these groups (P＜0.05).S100β protein expression was decreased when compared with the other two experimental groups at 7.5 h,and there was,significant difference (P＜0.05).Conclusions For the moderate bilateral carotid stenosis rabbit model,the expressions of NSE and S100β protein are both increased when blood pressure is reduced by 20％-30％ induced by bloodletting,nitroglycerin and narcotic drugs.The increase degree in propofol group is relatively light,which may be related to the cerebral protective effects of propofol. Key words: Bilateral carotid stenosis; Rabbits; Hypotension; Neuron-specific enolase; S100β

Bovine Spongiform Encephalopathy Induces Misfolding of Alleged Prion-Resistant Species Cellular Prion Protein without Altering Its Pathobiological Features

Bovine spongiform encephalopathy (BSE) prions were responsible for an unforeseen epizootic in cattle which had a vast social, economic, and public health impact. This was primarily because BSE prions were found to be transmissible to humans. Other species were also susceptible to BSE either by natural infection (e.g., felids, caprids) or in experimental settings (e.g., sheep, mice). However, certain species closely related to humans, such as canids and leporids, were apparently resistant to BSE. In vitro prion amplification techniques (saPMCA) were used to successfully misfold the cellular prion protein (PrP(c)) of these allegedly resistant species into a BSE-type prion protein. The biochemical and biological properties of the new prions generated in vitro after seeding rabbit and dog brain homogenates with classical BSE were studied. Pathobiological features of the resultant prion strains were determined after their inoculation into transgenic mice expressing bovine and human PrP(C). Strain characteristics of the in vitro-adapted rabbit and dog BSE agent remained invariable with respect to the original cattle BSE prion, suggesting that the naturally low susceptibility of rabbits and dogs to prion infections should not alter their zoonotic potential if these animals became infected with BSE. This study provides a sound basis for risk assessment regarding prion diseases in purportedly resistant species.

Tetramethylpyrazine decreases hypothalamic glutamate, hydroxyl radicals and prostaglandin-E2 and has antipyretic effects

We studied the effects of tetramethylpyrazine (TMP) on the fever, increased plasma levels of tumor necrosis factor-α (TNF-α) and increased hypothalamic levels of glutamate, hydroxyl radicals and prostaglandin-E2 (PGE2) induced by lipopolysaccharide (LPS). The microdialysis probes were stereotaxically and chronically implanted into the hypothalamus of rabbit brain for determining extracellular levels of glutamate, hydroxyl radials, and PGE2. In addition, both the body core temperature and plasma levels of TNF-α were measured. All the body core temperature, plasma levels of TNF-α, and hypothalamic levels of glutamate, hydroxyl radicals, and PGE2 were up-graded by an intravenous dose of LPS (2μg/kg). Pretreatment with intravenous TMP (10-40mg/kg) or intracerebroventricular TMP (130μg in 20μl per animal) 1h before LPS administration significantly attenuated the LPS-induced fever as well as the increased hypothalamic levels of glutamate, hydroxyl radicals, and PGE2. LPS-induced fever could also be attenuated by intravenous or intracerebroventricular TMP 1h after LPS injection. TMP preconditioning may cause its antipyretic action by reducing plasma levels of TNF-α as well as hypothalamic levels of glutamate, hydroxyl radicals, and PGE2 in rabbits.

Copper induces the accumulation of amyloid-beta in the brain

Accumulation of amyloid beta protein (Aβ) plays a major role in the etiology of Alzheimer’s disease (AD). Aβ is generated from the cleavage of amyloid precursor protein (APP) by beta-site APP-cleaving enzyme 1 (BACE1). There are two factors that reduce of Aβ accumulation in the brain; degradation by peptidases such as neprilysin (NEP) and clearance via two transporters. The low-density lipoprotein receptor related protein 1 (LRP1) is the major transporter that clears Aβ from brain to blood and the receptor for advanced glycation end products (RAGE) is a receptor that transports Aβ from blood to brain. Copper (Cu) has been postulated to play a role in the pathogenesis of AD, especially involved in Aβ aggregation and toxicity. According to a recent study, Cu(II) could reduce Aβ clearance from the brain in cholesterol-fed rabbits. However, the critical mechanism is unclear. This study was purposed to demonstrate whether Cu (II) would alter accumulation of Aβ in brain. We treated 25 and 50 μM CuSO4 for 48-hour in the well-defined neurodevelopmental cell line (PC12), rat choroidal epithelial cell line (Z310), and rat brain endothelial cell line (RBE4) to estimate the effects on Cu(II) exposure in the brain.

The science and clinical translation of remote postconditioning

The treatment of reperfusion injury requires measures beyond timely reperfusion. Conventional postconditioning (PostC) of ischemic tissues offers a strategy to reduce reperfusion injury, but its adoption is challenged by requiring access and imposing additional ischemia to the ischemic organ. Generating protective signals by PostC in a tissue remote from the target organ such as the limb, i.e. remote PostC (rPostC), may present an alternative approach to exerting endogenous tissue protection. Because rPostC is only recently reported, the fundamental biology of rPostC is not well understood, and studies to date are largely observational. rPostC has been observed to reduce ischemia-reperfusion injury experimentally in heart, kidney, brain and skeletal muscle in multiple species, including rat, rabbit and pig. Both necrosis and apoptosis are reduced. As in remote ischemic preconditioning, rPostC requires a transfer or communication of protective factors or signals through humoral and/or neural pathways. Triggers of target organ protection include G-protein-coupled receptor ligands, metabolites of ischemia, or small thermolabile molecules. Some evidence suggests that reperfusion injury salvage kinases may be involved in rPostC, in agreement with both preconditioning and conventional PostC. Clinical studies investigating improvements in clinical outcomes or biomarkers with rPostC are encouraging.

Bovine herpesvirus-5 infection in a rabbit experimental model: Immunohistochemical study of the cellular response in the CNS

Since little information is available regarding cellular antigen mapping and the involvement of non-neuronal cells in the pathogenesis of bovine herpesvirus type 5 (BHV-5) infection, it were determined the BHV-5 distribution, the astrocytic reactivity, the involvement of lymphocytes and the presence of matrix metalloproteinase (MMP)-9 in the brain of rabbits experimentally infected with BHV-5. Twelve New Zealand rabbits that were seronegative for BHV-5 were used for virus inoculation, and five rabbits were used as mock-infected controls. The rabbits were kept in separate areas and were inoculated intranasally with 500 μl of virus suspension (EVI 88 Brazilian isolate) into each nostril (virus titer, 107.5 TCID50). Control rabbits were inoculated with the same volume of minimum essential medium. Five days before virus inoculation, the rabbits were submitted to daily administration of dexamethasone. After virus inoculation, the rabbits were monitored clinically on a daily basis. Seven rabbits showed respiratory symptoms and four animals exhibited neurological symptoms. Tissue sections were collected for histological examination and immunohistochemistry to examine BHV-5 antigens, astrocytes, T and B lymphocytes and MMP-9. By means of immunohistochemical and PCR methods, BHV-5 was detected in the entire brain of the animals which presented with neurological symptoms, especially in the trigeminal ganglion and cerebral cortices. Furthermore, BHV-5 antigens were detected in neurons and/or other non-neural cells. In addition to the neurons, most infiltrating CD3 T lymphocytes observed in these areas were positive for MMP-9 and also for BHV-5 antigen. These infected cells might contribute to the spread of the virus to the rabbit brain along the trigeminal ganglia and olfactory nerve pathways.

Efficacy of L-carnosine against Schistosoma mansoni antigens in liver, heart, kidney and brain of rabbits

Article history: The present investigation was an attempt to study the enhancememt effect of L-carnosine (beta alanyl-l-histidine) on the influence of vaccination on healthy (non-infected) rabbits treated with Schistosoma mansoni egg antigens, cercariae antigens, and worms antigens as protective agents against infection. This study involved individual injection of three Schistosoma mansoni antigens: soluble egg antigen (SEA), cercarial antigen preparation (CAP) and soluble worm antigen preparation (SWAP), in three rabbit groups, respectively. Three other groups each received the same specific antigen in conjunction with the administration of L-carnosine, biochemical parameters including DNA, RNA, DNA/RNA ratio concentrations in addition ATPase, and acetyl cholinesterase activities were measured in liver, heart, kidney and brain in all groups. Elevation in most parameters was observed in the immunized groups. Carnosine treatment of rabbit groups immunized with SEA, CAP and SWAP in comparison to the non-carnosine-treated immunized groups resulted in amelioration the changes of DNA, RNA, ATPase and acetyl cholinesterase activities in most groups. L-carnosine has a beneficial effect in the amelioration of the changes in biochemical parameters as a result of S. mansoni antigen immunization.

Effects of &lt;i&gt;Hibiscus &lt;/i&gt;&lt;i&gt;S&lt;/i&gt;&lt;i&gt;abdariffa&lt;/i&gt; Extracts on 2, 4-Dinitrophenylhydrazine-induced Cytotoxicity in Rabbits

This study examines the effects of aqueous and anthocyanin-rich extracts of Hibiscus sabdariffa calyces on 2,4-din itrophenylhydrazine (DNPH)-induced biochemical changes in the blood, brain and liver of rabbits. Changes in tissue levels of glucose and protein were used as indices of alteration and p rotection. Thirty male adult rabbits used for the study were d ivided into six groups. Group 1, the control took only water wh ile animals in groups 2,3,5 and 6 received 100 mg/kg body weight of the extracts once daily for 28 days. After 22 nd day of treat ment, the rabbits in groups 4, 5 and 6 received 28 mg/kg body weight of DNPH for the remaining 5 days of treat ment, after which the animals were sacrificed. Relative to control, animals treated with DNPH alone (Group 4) showed significant (p<0.05) reduction in the levels of glucose and protein in the tissues. However, animals treated with each of the aqueous extract and anthocyanin-rich ext ract prior to DNPH administration (Groups 5 and 6), showed no significant alterat ion in the tissue levels of these parameters. Our findings show that extracts of the Hibiscus sabdariffa contain phytochemicals that effectively amelio rate 2, 4-din itrophenylhydrazine-induced cytotoxicity in rabbits.

The detection of chronic cerebral hemorrhage in rabbits with magnetic induction

Chronic cerebral hemorrhage (CCH) in the brain is an important clinical problem that is often monitored and studied with expensive devices such as MRI and PET, which are not readily available in low economical resource parts of the world. We have developed a less expensive tool for non-contact monitoring of CCH in the brain. The system measures the phase shift between the electromagnetic signals on the two coils. CCH was induced in the brain of rabbits by stereotactic method. Intracranial pressure (ICP) and Electrocardiograph (ECG) of subjects were monitored for 1.5h. Signals were continuously monitored up to t=1.5h at exciting frequency 10.7MHz. From 0.8 to 2.4 ml of autologous blood was injected (each injection quantity of 0.8 ml, the interval time for 30 minutes). The results show significant phase shifts increase as a function of injection volume. ICP and phase shift were directly proportional to the related, while HRV were stable around 200beats*min-1. Our system has high sensitivity that even 0.8 ml can also be detected. In this study, the curves of inductive phase shift are significantly related to ICP. This observation suggests that the method could be valuable, in addition to continuous monitoring, also for early warning in emergency medicine and critical care units.

Central Nervous System Disposition and Metabolism of Fosdevirine (GSK2248761), a Non-Nucleoside Reverse Transcriptase Inhibitor: An LC-MS and Matrix-Assisted Laser Desorption/Ionization Imaging MS Investigation into Central Nervous System Toxicity

The CNS disposition and metabolism of Fosdevirine (FDV), an HIV non-nucleoside reverse transcriptase inhibitor, was investigated in four patients who unexpectedly experienced seizures after at least 4 weeks of treatment in a Phase IIb, HIV-1 treatment experienced study. In addition, the CNS disposition and metabolism of FDV was examined in samples from rabbit, minipig, and monkey studies. LC-MS was used to characterize and estimate the concentrations of FDV and its metabolites in cerebral spinal fluid (seizure patients, rabbit, and monkey) and brain homogenate (rabbit, minipig, and monkey). The application of matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) provided the spatial distribution of FDV and its metabolites in brain tissue (rabbit, minipig, and monkey). A cysteine conjugate metabolite resulting from an initial glutathione (GSH) Michael addition to the trans-phenyl acrylonitrile moiety of FDV was the predominant drug-related component in the samples from seizure patients, rabbits, and minipigs. This metabolite persisted in the CNS for an extended period of time after the last dose in both seizure patients and minipigs. Furthermore, the localization of this metabolite was found to be highly associated with the white matter in rabbit and minipig brain sections by MALDI IMS. In contrast, the predominant component in monkey CNS was FDV, which was shown to be highly associated with the gray matter. On the basis of these data, several hypothesizes are considered, which might provide insights into species differences in CNS toxicity/seizures observed after FDV dosing.

Risperidone Microemulsion for Transnasal Delivery: Pharmacodynamic and Pharmacokinetic Evaluation

The present study describes development and evaluation of risperidone (RPD) microemulsions (RME) for transnasal delivery in the treatment of schizophrenia. The RME was prepared by the titration method and characterized for physicochemical parameters. Pharmacodynamic evaluations (apomorphine – induced compulsive behavior and spontaneous locomotor activity) were performed using mice. All formulations were radiolabeled with 99mTc (technetium) and biodistribution of drug in the brain was studied using Swiss albino rats. Brain scintigraphy imaging in rabbits was also performed to ascertain the uptake of the drug into the brain. RME were transparent and stable with mean globule size of 15- 30 nm and zeta potential of -30mV to -40mV. In pharmacodynamic studies, significant (P<0.05) variation in parameters estimated, were found between the treated and control groups. 99mTc-labeled risperidone solution (RS)/RME/RPD mucoadhesive microemulsion (RMME) were found to be stable and suitable for in vivo studies. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of RMME compared to intravenous RME was found to be 6 to 8 fold higher indicating larger extent of distribution of the drug in brain. Drug targeting efficiency, and direct drug transport were found to be highest for RMME post-intranasal administration compared to intravenous RME. Rabbit brain scintigraphy also showed higher intranasal uptake of the drug into the brain. This investigation demonstrates a more rapid and larger extent of transport of risperidone into the brain with intranasal RMME, which may prove useful for treatment of schizophrenia. Keywords: Brain scintigraphy, microemulsion, pharmacokinetic study, pharmacodynamic study, risperidone.

Risperidone Microemulsion for Transnasal Delivery: Pharmacodynamic and Pharmacokinetic Evaluation

The present study describes development and evaluation of risperidone (RPD) microemulsions (RME) for transnasal delivery in the treatment of schizophrenia. The RME was prepared by the titration method and characterized for physicochemical parameters. Pharmacodynamic evaluations (apomorphine – induced compulsive behavior and spontaneous locomotor activity) were performed using mice. All formulations were radiolabeled with 99mTc (technetium) and biodistribution of drug in the brain was studied using Swiss albino rats. Brain scintigraphy imaging in rabbits was also performed to ascertain the uptake of the drug into the brain. RME were transparent and stable with mean globule size of 15- 30 nm and zeta potential of -30mV to -40mV. In pharmacodynamic studies, significant (P<0.05) variation in parameters estimated, were found between the treated and control groups. 99mTc-labeled risperidone solution (RS)/RME/RPD mucoadhesive microemulsion (RMME) were found to be stable and suitable for in vivo studies. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of RMME compared to intravenous RME was found to be 6 to 8 fold higher indicating larger extent of distribution of the drug in brain. Drug targeting efficiency, and direct drug transport were found to be highest for RMME post-intranasal administration compared to intravenous RME. Rabbit brain scintigraphy also showed higher intranasal uptake of the drug into the brain. This investigation demonstrates a more rapid and larger extent of transport of risperidone into the brain with intranasal RMME, which may prove useful for treatment of schizophrenia. Keywords: Brain scintigraphy, microemulsion, pharmacokinetic study, pharmacodynamic study, risperidone.

Abstract 98: New Technique of Gas Adiabatic Expansion for Brain and General Hypothermia in Rabbit

Background: Irreversible brain damage is a major issue in the acute treatment of OHCA. Brain protection by fossa nasalis cooling on the field has been reported. We propose a new technique to produce cooling by adiabatic gas expansion. Preliminary in vitro and animal studies have demonstrated that Carbon Dioxyde was able to produce significant cooling. The purpose of this work was to quantify the amount of cooling produced by this method on a rabbit model. Method: Study population consisted of 8 New-Zealand rabbits 3.5 kg studied under ketamine anesthesia without ventilation. Three lead ECG were displayed and sampled. Temperatures in °C, were measured by thermocouples every minute: close to the injector exit located inside a 12mm Ø, 2mm thick PVC canula inserted in the mouth up to the oropharynx, in the mouth close to the canula, in the nasopharynx (equivalent to tympanic) and in the rectum. Temperature curves were displayed on line on a computer screen. Data were processed by Statistica v6.0. A p value ≤ 0.05 was considered as significant. After stabilization of temperatures, gas regulated at around 500 psi was delivered during a period of 13 ± 2.7 min and expanded at the exit of the injector. Results: The initial 90% drop of temperature was obtained near the injector in 3 ± 1.47 minutes. The table below compares the temperatures recorded at the Start of cooling and at the End of this experiment. A significant low temperature was observed near the injector (-16.9°C), the nasopharynx (37.7°C) and the oropharynx (31.2°C). A tendency not reaching statistical significance was obtained on the core temperature (39.4°C). No adverse side effect was observed during and after the experiment especially no injury to the throat by direct visual inspection. Discussion: Core temperature drop was similar to that reported in pigs after nasopharynx PFC evaporation (Yu et al Crit Care Med. 2010). The lowest temperature (-16.9°C) was recorded as expected at the exit of gas, however, oral and nasal temperatures remained within tolerable values. Stronger effect on nasal temperature can be due to better mechanical contact of the canula against the upper oropharynx wall. Non-significant core cooling was probably due to the limit imposed by distance despite normal blood circulation. Nevertheless, a clear tendency was obtained as previously observed with other techniques of fossa nasalis cooling. Conclusion: This study demonstrates for the first time that carbon dioxyde adiabatic expansion in the mouth is effective for brain and body hypothermia in a rabbit model. This new technique which is simple, not expensive and easy to use by a lay person opens new vistas for the treatment of OHCA which can be started intra-arrest before CPR.

99mTc-Daunorubicin a potential brain imaging and theranostic agent: synthesis, quality control, characterization, biodistribution and scintigraphy

Daunorubicin is a chemotherapeutic antibiotic of the anthracycline family used for the treatment of many type of cancers when doxorubicin or other less effective drugs cannot be used. The aim of the present study was labeling of Daunorubicin with (99m)Tc, quality control, characterization, and biodistribution of radiolabeled Daunorubicin. Labeling efficiency was determined by ascending paper chromatography. All the experiments were performed at room temperature (25°C±2°C). More than 96% labeling efficiency with (99m)Tc was achieved at pH 5-6, 2-4 μg stannous chloride and 300 μg of ligand in few minutes. The characterization of the compound was performed by using HPLC, electrophoresis and shake flask assay. Electrophoresis indicates that Tc-99m-Daunorubicin is neutral, HPLC confirms the single specie of the labeled compound, while shake flask assay confirms high lipophilicity. The biodistribution studies of (99m)Tc-Daunorubicin were performed in rats. Significantly higher accumulation of (99m)Tc-Daunorubicin was seen in brain of normal rats. Scintigraphy was also indicating higher accumulation of (99m)Tc-Daunorubicin in brain of normal rabbits.

Homozygous FVII deficiencies with different reactivity towards tissue thromboplastins of different origin

The reagents most frequently used for FVII activity assay are obtained by rabbit brain or human placenta. In recent years, human recombinant thromboplastins have received great attention. FVII activity in FVII deficiency is usually low, regardless of the thromboplastin used. There are a few exceptions to this rule. These are represented by FVII Padua (Arg304Gln), FVII Nagoya (Arg304Trp), and FVII (Arg79Gln). In these three instances, clear discrepancies were noted in the FVII activity depending on the thromboplastin used. This indicates that at least two areas of FVII are involved in tissue binding, namely an epidermal growth factor domain of the light chain (Arg79Gln) and the catalytic domain (Arg304), controlled by exons 4 and 8, respectively. Since these three variants are cross reactive material positive, namely they are Type 2 defects, all other variants with normal antigen should be investigated by a panel of at least three tissue thromboplastins (rabbit brain, human tissue or human recombinant, and ox brain derived) in order to obtain a satisfactory classification.

Dynamics of the Assimilation of an Imposed Rhythm by Neuron Assemblies in the Sensorimotor and Visual Cortical Areas of the Rabbit Brain

The linked activity of pairs of neurons in the sensorimotor and visual zones of the cortex was analyzed in naive rabbits, rabbits being trained, and trained rabbits during formation of a latent rhythmic focus of excitation (defensive dominant) in the central nervous system. During formation of the dominant in the cortex, there was a progressive increase in the proportion of neuron pairs whose linked activity was dominated by the rhythm applied by the experimental stimulation. In the sensorimotor zone of the cortex of trained rabbits, as compared with untrained animals, there were significantly greater proportions of pairs of both close-lying and distant neurons, whose linked activity was dominated by the rhythm imposed during stimulation. In the visual zone of the cortex, a significantly greater proportion of these pairs was see only when distant neurons were studied. Analysis of the interactions of neurons in the sensorimotor and visual areas of the cortex also revealed training-associated increases in the numbers of pairs with the activity rhythm imposed during the experiment when the influences of sensorimotor cortex neurons on visual cortex neurons and vice versa were analyzed.

Animal Models of brain central herniation

Objective To establish a model of brain central herniation and simulate the clinical situation.Methods The rabbit brain central herniation model was established through inflating a balloon in the bottom of the frontal lobe,and combined with the characteristics of clinical stage to observe changes in intracranial pressure,cerebral perfusion pressure,vital signs,imaging and pathology after the formation of cerebral hernia.Results After establishment of central herniation model,the changes of observed indexes were significant and consisted with the clinical symptoms in each period.Conclusion This model can be used to establish and definite each stage of the brain central hernia,and lays a foundation of further research of center hernia about mechanisms of pathophysiology,clinical treatment and prognosis. Key words: Encephalocele; Models, animal; Intracranial hypertension; Pathology