Rat Brain Research Articles

Highly Sensitive and Biocompatible Microsensor for Selective Dynamic Monitoring of Dopamine in Rat Brain.

Highly selective and sensitive in vivo neurotransmitter dynamic monitoring of the central nervous system has long been a challenging endeavor. Here, an implantable and biocompatible microsensor with excellent performances was reported by electrodepositing poly(3,4-ethylenedioxythiophene)-electrochemically reduced graphene oxide (PEDOT-ERGO) nanocomposites and poly(tannic acid) (pTA) sequentially on the carbon fiber electrode (CFE) surface, and its feasibility in in vivo electrochemical sensing applications were demonstrated. Due to the synergistic electrocatalytic effect of PEDOT-ERGO nanocomposites with the negative-charged pTA on dopamine (DA) redox reaction, the microsensor exhibits high detection sensitivities of 1.1 and 0.37 nA μM-1 in the detection ranges of 0.02-0.5 and 0.5-20 μM with a low limit of detection of 9.2 nM. Also, the microsensor shows excellent selectivity, good sensing stability, repeatability, and reproducibility. In addition, the highly hydrophilic and negative-charged pTA inhibits the nonspecific adsorption of hydrophobic proteins, which endows the microsensor with good antifouling ability. Moreover, DA dynamics in rat brain were successfully monitored in real time, and the selective sensing ability of the microsensor in vivo was also demonstrated. The present study provides a new method for selective dynamics monitoring of DA in the brain, which would help to better understand the pathological and physiological functions of DA.

Simultaneous assessment of cerebral glucose and oxygen metabolism and perfusion in rats using interleaved deuterium (2H) and oxygen-17 (17O) MRS.

Cerebral glucose and oxygen metabolism and blood perfusion play key roles in neuroenergetics and oxidative phosphorylation to produce adenosine triphosphate (ATP) energy molecules in supporting cellular activity and brain function. Their impairments have been linked to numerous brain disorders. This study aimed to develop an in vivo magnetic resonance spectroscopy (MRS) method capable of simultaneously assessing and quantifying the major cerebral metabolic rates of glucose (CMRGlc) and oxygen (CMRO2) consumption, lactate formation (CMRLac), and tricarboxylic acid (TCA) cycle (VTCA); cerebral blood flow (CBF); and oxygen extraction fraction (OEF) via a single dynamic MRS measurement using an interleaved deuterium (2H) and oxygen-17 (17O) MRS approach. We introduced a single-loop multifrequency radio-frequency (RF) surface coil that can be used to acquire proton (1H) magnetic resonance imaging (MRI) or interleaved low-γ X-nuclei 2H and 17O MRS. By combining this RF coil with a modified MRS pulse sequence, 17O-isotope-labeled oxygen gas inhalation, and intravenous 2H-isotope-labeled glucose administration, we demonstrate for the first time the feasibility of simultaneously and quantitatively measuring six important physiological parameters, CMRGlc, CMRO2, CMRLac, VTCA, CBF, and OEF, in rat brains at 16.4T. The interleaved 2H-17O MRS technique should be readily adapted to image and study cerebral energy metabolism and perfusion in healthy and diseased brains.

Organ toxicities associated with diet-induced obesity in rats: Investigation of changes in activities selected enzymes.

Obesity stands out as one of the most significant health problems in the modern world. The prevalence of high-calorie diets (HCDs) globally exacerbates this condition. Throughout history, plants and plant-derived food products have been utilized for medicinal purposes, demonstrating their efficacy in the treatment and prevention of various diseases. Gundelia tournefortii (GT), a plant of interest, is known to possess beneficial properties. Hence, this study aimed to investigate the immunotoxic and neurotoxic effects of two different doses of GT plant extract on the liver, brain, and heart tissues of obese rats. For this purpose, Wistar male rats were divided into four groups: "CG," "HCDG," "HCDGUN1," and "HCDGUN2" At the conclusion of the study, adenosine deaminase (ADA) and myeloperoxidase (MPO) activities, as well as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) biomarkers, were evaluated in the liver, heart, and brain tissues. The study results revealed a statistically significant increase in ADA and MPO activities in the HCDG group compared to the CG group, alongside a significant decrease in the HCDGUN groups compared to the HCDG group. Regarding AChE and BChE activities, a statistically significant decrease was observed in the HCDG group compared to the CG group, whereas an increase was noted in the HCDGUN groups relative to the HCDG group, with the latter approaching values similar to those of the control group. In conclusion, the intake of GT plant extract exhibited positive effects on the immunotoxic and neurotoxic effects induced by HCD in rats with an experimental obesity model, as evidenced by tissue biomarker evaluations.

Shifts in the spatiotemporal profile of inflammatory phenotypes of innate immune cells in the rat brain following acute intoxication with the organophosphate diisopropylfluorophosphate

Acute intoxication with cholinesterase inhibiting organophosphates (OP) can produce life-threatening cholinergic crisis and status epilepticus (SE). Survivors often develop long-term neurological consequences, including spontaneous recurrent seizures (SRS) and impaired cognition. Numerous studies implicate OP-induced neuroinflammation as a pathogenic mechanism contributing to these chronic sequelae; however, little is known about the inflammatory phenotype of innate immune cells in the brain following acute OP intoxication. Thus, the aim of this study was to characterize the natural history of microglial and astrocytic inflammatory phenotypes following acute intoxication with the OP, diisopropylfluorophosphate (DFP). Adult male and female Sprague–Dawley rats were administered a single dose of DFP (4 mg/kg, sc) followed by standard medical countermeasures. Within minutes, animals developed benzodiazepine-resistant SE as determined by monitoring seizures using a modified Racine scale. At 1, 3, 7, 14, and 28 d post-exposure (DPE), neuroinflammation was assessed using translocator protein (TSPO) positron emission tomography (PET) and magnetic resonance imaging (MRI). In both sexes, we observed consistently elevated radiotracer uptake across all examined brain regions and time points. A separate group of animals was euthanized at these same time points to collect tissues for immunohistochemical analyses. Colocalization of IBA-1, a marker for microglia, with iNOS or Arg1 was used to identify pro- and anti-inflammatory microglia, respectively; colocalization of GFAP, a marker for astrocytes, with C3 or S100A10, pro- and anti-inflammatory astrocytes, respectively. We observed shifts in the inflammatory profiles of microglia and astrocyte populations during the first month post-intoxication, largely in hyperintense inflammatory lesions in the piriform cortex and amygdala regions. In these areas, iNOS+ proinflammatory microglial cell density peaked at 3 and 7 DPE, while anti-inflammatory Arg1+ microglia cell density peaked at 14 DPE. Pro- and anti-inflammatory astrocytes emerged within 7 DPE, and roughly equal ratios of C3+ pro-inflammatory and S100A10+ anti-inflammatory astrocytes persisted at 28 DPE. In summary, microglia and astrocytes adopted mixed inflammatory phenotypes post-OP intoxication, which evolved over one month post exposure. These activated cell populations were most prominent in the piriform and amygdala areas and were more abundant in males compared to females. The temporal relationship between microglial and astrocytic responses suggests that initial microglial activity may influence delayed, persistent astrocytic responses. Further, our findings identify putative windows for inhibition of OP-induced neuroinflammatory responses in both sexes to evaluate the therapeutic benefit of anti-inflammation in this context.

Discovery of 18F Labeled AZD5213 Derivatives as Novel Positron Emission Tomography (PET) Radioligands Targeting Histamine Subtype-3 Receptor.

The histamine subtype 3 (H3) receptor is an important drug target in the central nervous system (CNS), and PET imaging offers a promising technique for the noninvasive evaluation of CNS disease related to the H3 receptor. In this study, we synthesized and evaluated the binding effects of [18F]H3-2404 and [18F]H3-2405 by modifying the structure of AZD5213, a selective H3 antagonist. These two radioligands were prepared in high radiochemical yields and displayed stability in serum. The in vitro autoradiographic study in rat brain tissue and the following in vivo PET studies in mice demonstrated sufficient brain uptake but predominantly non-specific distribution in rodent brain. Although these data suggest that [18F]H3-2404 and [18F]H3-2405 are unsuitable as PET tracers for brain imaging of the H3 receptor, this study provides a valuable attempt for optimizing 18F labeled radiotracers based on AZD5213.

LY354740, an agonist of glutamatergic metabotropic receptor mGlu2/3 increases the cytochrome P450 2D (CYP2D) activity in the frontal cortical area of rat brain.

Our previous studies indicated that changes in the functioning of the brain glutamatergic system involving the NMDA receptor may affect cytochrome P450 2D (CYP2D) in the brain. Since CYP2D may contribute to the metabolism of neurotransmitters and neurosteroids engaged in the pathology and pharmacology of neuropsychiatric diseases, in the present work we have investigated the effect of compound LY354740, an agonist of glutamatergic metabotropic receptor mGlu2/3, on brain and liver CYP2D. The activity (high performance liquid chromatography with fluorescence detection) and protein levels (Western blotting) of CYP2D were measured in the microsomes from the liver and different brain areas of male Wistar rats after 5day-treatment with LY354740 (10mg/kg ip). The results were analyzed statistically using Student's t-test. Among the investigated brain areas, the highest CYP2D activity was found in the cerebellum and brainstem, which exceeded that in the thalamus, cortex, hippocampus and frontal cortex. The mGlu2/3 receptor agonist LY354740 administered for five consecutive days significantly increased the protein level and activity of CYP2D in the frontal cortex. Such a tendency was also observed in the other brain areas. LY354740 did not affect the CYP2D activity in the liver. Repeated administration of the mGlu2/3 receptor agonist, the compound LY354740 specifically increases the protein level and activity of CYP2D in the frontal cortex, which may accelerate dopamine synthesis via an alternative CYP2D-mediated route in the mesocortical dopaminergic pathway, and thus may contribute to the beneficial pharmacological effect on negative symptoms of schizophrenia.

Photobiomodulation Therapy at 660 nm Inhibits Hippocampal Neuroinflammation in a Lipopolysaccharide-Challenged Rat Model

Background/Objectives: Neuroinflammation is associated with the progression of various brain diseases, and the management of neuroinflammation-induced neural damage is a crucial aspect of treating neurological disorders. This study investigated the anti-inflammatory efficacy of photobiomodulation therapy (PBMT) using 660 nm phototherapy in a rat model with lipopolysaccharide (LPS)-induced neuroinflammation. Methods: We induced inflammation in rat brains via intraperitoneal injection of LPS and subjected the treatment group to 660 nm phototherapy to examine its protective effect against hippocampal damage based on pathological, histological, and immunohistochemical tissue analyses. Results: The 660 nm treated rats showed a significant decrease in hippocampal structural damage and cell death compared to the LPS-treated group. We observed reduced expression of the inflammation markers GFAP, TNF-α, and IL-1β in the hippocampus of the treatment group, and an increase in SIRT1 expression across all hippocampal regions. Conclusions: This study presents a promising method for controlling neuroinflammation and providing neuroprotection and inflammation relief. PBMT represents a non-invasive therapeutic approach with minimal side effects ensured through the proper control of light irradiation.

The number and distribution of proliferating cells in the rat’s rostral migratory stream as identified by means of two different proliferation markers

ABSTRACT In the brains of adult rodents, the cells arising in the subventricular zone of the lateral ventricles maintain the ability to divide when migrating to the olfactory bulb along the rostral migratory stream (RMS). Dividing cells in the RMS are most frequently revealed through immunohistochemical detection of an exogenous marker of proliferation, 5-Bromo-2-deoxyuridine (BrdU), which incorporates into DNA during the S-phase of mitosis. The more recently recognized antigen Ki-67 (also known as Kiel-67 and MKI67), an endogenous protein expressed in nuclei at all stages of mitosis, is also used for proliferation detection. BrdU and Ki-67 are often used as alternative methods, but they have not previously been compared in the RMS. We analyzed the numbers and distribution of cells labeled either with BrdU or Ki-67 within the RMS of adult rats. The first group of animals received a single i.p. dose of BrdU. In the second group, dividing cells were visualized by Ki-67 immunohistochemistry. Some sections from brains of BrdU-treated rats were also immunostained for Ki-67. Labeled cells were counted in the three anatomical parts of the RMS (vertical arm, elbow and horizontal arm) using a method for unbiased estimation of cell density. The distribution of proliferating cells was similar for both markers. Most BrdU and Ki-67 positive cells were located in the vertical arm and in the elbow, but a caudo-rostral reduction in cell divisions was more evident with Ki-67 labeling. The number of Ki-67 positive cells significantly exceeded the number of BrdU positive cells in all parts of the RMS. Our results indicate that BrdU and Ki-67 are not interchangeable markers for evaluation of proliferative activity in the RMS.

Neuroprotective Effects of Curcumin against Chronic Chlorpyrifos- Induced Oxidative Damage in Rat Brain Tissue.

Chlorpyrifos (CPF) is an organophosphate pesticide that inhibits acetylcholinesterase (AChE) activity. Investigations have also focused on its neurotoxicity, which is independent of AChE inhibition. Here, we evaluated the effect of CPF on oxidative indices in the brain tissue and explored the protective effect of curcumin (Cur) against its toxicity. Forty male Wistar rats were divided into five groups, each consisting of eight rats (n = 8) per group. Animals were administrated by oral gavage for 90 days with the following treatments: control (C), CPF, CPF + CUR 25 mg/kg, CPF + CUR50, and CPF + cur 100 received olive oil, CPF, CPF plus 25 mg/kg of CUR, CPF plus 50 mg/kg of CUR, and CPF plus 100 mg/kg of CUR, respectively. After anesthetization, animal brain tissues were obtained for assessment of oxidative stress indices. The concentration of MDA significantly increased in the brains of the CPF group as compared to the control group (p < 0.01). Also, a significant decrease in MDA concentrations was observed in the brains of rats in the CPF + Cur 100 group compared to the CPF group (p < 0.05). A significant decrease was noted in the GSH concentration in the brains of the CPF group compared to the control group (p < 0.05). Treatment with Cur at 100 mg/kg exhibited a significant increase in GSH concentrations in the brains of the CPF-exposed group compared to the CPF group without Cur administration (p < 0.05). The concentration of NO exhibited a significant increase in the brains of the CPF group when compared to the control group (p < 0.05). Also, a significant decrease in NO concentration was observed in the brain tissue of the CPF + Cur 100 group compared to the CPF group (p < 0.05). Our data establish that chronic exposure to CPF induced oxidative stress in brain tissue, which was reversed by CUR administration. Additional experimental and clinical investigations are needed to validate the efficacy of CUR as a potential antidote for CPF poisoning.

Sleep and diurnal alternative polyadenylation sites associated with human APA-linked brain disorders

Disruption of sleep and circadian rhythms are a comorbid feature of many pathologies, and can negatively influence many health conditions, including neurodegenerative disease, metabolic illness, cancer, and various neurological disorders. Genetic association studies linking sleep and circadian disturbances with disease susceptibility have mainly focused on changes in gene expression due to mutations, such as single-nucleotide polymorphisms. The interaction between sleep and/or circadian rhythms with the use of Alternative Polyadenylation (APA) has been largely undescribed, particularly in the context of other disorders. APA generates transcript isoforms by utilizing various polyadenylation sites (PASs) from the same gene affecting its mRNA translation, stability, localization, and subsequent function. Here we identified unique APAs expressed in rat brain over time-of-day, immediately following sleep deprivation, and the subsequent recovery period. From these data, we performed a secondary analysis of these sleep- or time-of-day associated PASs with recently described APA-linked human brain disorder susceptibility genes.

Investigation of Antioxidant and Anti-inflammatory Properties of Berberine Nanomicelles: In vitro and In vivo Studies.

In the present study, neuroprotective effects of berberine (BBR) and berberine nanomicelle (BBR-NM) against lipopolysaccharides (LPS)-induced stress oxidative were investigated, and compared by evaluating their antioxidant and anti-inflammatory activities in PC12 cells, and rat brains. A fast, green, and simple synthesis method was used to prepare BBR-NMs. The prepared BBR-NMs were then characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). In vitro experiments were carried out on the LPS-treated PC12 cell lines to investigate the anti-cytotoxic and antioxidant properties of BBR-NM and BBR. The results showed that BBR-NMs with a diameter of ~100 nm had higher protective effects against ROS production and cytotoxicity induced by LPS in PC12 cells in comparison with free BBR. Moreover, in vivo experiments indicated that the activity levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), increased in the brain of LPS-treated rats administrated with BBR-NM at the optimum dose of 100 mg.kg-1. BBR-NM administration also resulted in decreased concentration of lipid peroxidation (MDA) and pro-inflammatory cytokines, such as Serum interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). Overall, BBR-NM demonstrated higher neuroprotective effects than free BBR, making it a promising treatment for improving many diseases caused by oxidative stress and inflammation.

Comparison of forced and voluntary exercise types on male rat brain monoamine levels, anxiety-like behaviour, and physiological indexes under light and dark phases

Comparison of forced and voluntary exercise types on male rat brain monoamine levels, anxiety-like behaviour, and physiological indexes under light and dark phases

Implanting a Wireless Bidirectional Microelectrode System in a Rat Brain

Implanting a Wireless Bidirectional Microelectrode System in a Rat Brain

Implanting a Wireless Bidirectional Microelectrode System in a Rat Brain

Implanting a Wireless Bidirectional Microelectrode System in a Rat Brain

Drug Microinjection with Electrophysiological Recording in a Rat Brain

Drug Microinjection with Electrophysiological Recording in a Rat Brain

Drug Microinjection with Electrophysiological Recording in a Rat Brain

Drug Microinjection with Electrophysiological Recording in a Rat Brain

Label-free rat brain traumatic penumbra imaging based on multiphoton fluorescence microscopy

Label-free rat brain traumatic penumbra imaging based on multiphoton fluorescence microscopy

Determination of Astrocyte Reaction Using Glial Fibrillary Acidic Protein (GFAP) Following Aluminium Chloride Induced Hippocampus Damage of Adult Wistar Male Rats Treated with Ethanolic Extracts of Carpolobia lutea at Different Doses

Background: Aluminium is a well-established neurotoxicant involved in the etiology of neurodegenerative diseases. Carpolobia lutea, commonly called cattle stick or poor man’s candle belongs to the plant family polygalaceae. It is a small tree native to West and Central tropical Africa and it is one of the medicinal plants that play a major role in the health care system of developing countries such as Nigeria. Aim of the Study: This study was aimed at investigating astrocyte reaction in aluminium chloride induced neurotoxicity in the hippocampus in adult male wistar rats treated with ethanolic extracts of C.lutea at different doses. Materials and Methods: Thirty wistar rats weighing 180-200 g were used for this study. The animals were randomized into five groups of six rats each. Group A rats received only animal feed. Groups B,C,D and E were given 100 mg/kg bw of aluminium chloride intraperitoneally five times a week for three weeks to induce neurotoxicity.In order to reverse the neurotoxicity,. Group C was treated with 10 mg/kg bw of donepezil as standard drug while group D and E were treated with 200 mg/kg and 400 mg/kg of Carpolobia lutea respectively for 14 days. Histopathological study was done on the hippocampus of the rat brain and thereafter hematoxylin and eosin staining were carried out. Immunohistochemical studies for GFAP was done using NovocasraTM Novolink TMpolymer detection system and appropriate primary monoclonal antibodies. Image J cell counter tool was used to note the number of GFAP positive cells across all groups. Results: The result from our histopatholological study shows that lower dose (200 mg/kg/bw) of ethanolic extract of the leaf of Carpolobia lutea have better protection on the cytoarchitecture of the CA1, CA3, and dentate gyrus of the hippocampus than 400 mg/kg/bw of the plant extract. From our study, it is evident that 200 mg/kg of Carpolobia lutea reduced the GFAP immunoreactivity in the hippocampus of AlCl3 induced neurotoxicity. When we compared the result of 200 mg/kg/bw of C. lutea with 10 mg/kg per body weight of donepezil (standard drug), it was observed that C. lutea had a slight reduced GFAP immunoreactivity than the standard drug(donepezil). The lower dose, 200 mg/kg of ethanolic extract of the leaf of Carpolobia lutea have a better neuroprotective benefit than the standard drug on the hippocampus Conclusion: In conlusion, 200 mg/kg of Carpolobia lutea have the tendencies of protecting the neurons in the hippocampus from degenerating as a result of aluminium chloride induced neurotoxicity compared to the standard drug (10 mg/kg donepezil).

The participation of monoamines in the realization of vasopressin analgesic effects during electrical stimulation of paws in rats

BACKGROUND: Arginine vasopressin has been implicated in the modulation of stress and pain. The influence of a synthetic analogue of arginine vasopressin, 1-deamino-8-D-arginine-vasopressin, оn pain sensitivity, stress reactivity, levels of monoamines and brain neurotrophic factor in a model of paw electrical stimulation in rats has not been studied. AIM: The aim was to evaluate the effect of a synthetic vasopressin analog, 1-deamino-8-D-arginine-vasopressin, on pain sensitivity and the content of norepinephrine, serotonin, dopamine, brain neurotrophic factor in the parietal cortex and spinal cord in electrocutaneous paw stimulation test in rats. MATERIALS AND METHODS: The study was conducted on male Wistar rats who were injected with 1-deamino-8-D-arginine-vasopressin intranasally once a day for 5 days in small (single 20 ng, course 100 ng) and large doses (single 2 ug, course 10 ug). The content of brain neurotrophic factor in the parietal cortex and spinal cord, and corticosterone in blood serum were determined using enzyme immunoassay. The levels of norepinephrine, serotonin, dopamine and their metabolites in the brain were evaluated using high-performance liquid chromatography. RESULTS: 1-Deamino-8-D-arginine-vasopressin in different doses reduced pain sensitivity in rats, more pronounced when administered in large doses. The peptide in small doses in the parietal cortex increased the content of dopamine and reduced the levels of 5-hydroxyindolacetic acid, a metabolite of serotonin; in the spinal cord, it reduced the content of 5-hydroxyindolacetic acid. 1-Deamino-8-D-arginine-vasopressin in high doses in the parietal cortex increased the content of dopamine and reduced the levels of 5-hydroxyindolacetic acid; in the spinal cord ― reduced the content of serotonin and 3,4-dihydroxyphenylacetic acid, a metabolite of dopamine; increased the levels of norepinephrine and homovanilic acid, a metabolite of dopamine. The peptide had no effect on corticosterone levels in the blood and brain neurotrophic factor levels in the brain in rats. CONCLUSIONS: The analgesic effects of 1-deamino-8-D-arginine-vasopressin were revealed with intranasal administration in different subendocrine doses. Regardless of the administered doses, dopamine and serotonin at the supraspinal level were involved in peptide-induced anesthesia; serotonin at the spinal cord level. More pronounced analgesia with the administration of 1-deamino-8-D-arginine-vasopressin in high doses was due to the additional involvement of dopamine and norepinephrine at the spinal cord level.

Saturation transfer (CEST and MT) MRI for characterization of U-87 MG glioma in the rat.

The focus of this work was to identify the optimal magnetic resonance imaging (MRI) contrast between orthotopic U-87 MG tumours and normal appearing brain with the eventual goal of treatment response monitoring. U-87 MG human glioblastoma cells were injected into the brain of RNU nude rats (n= 9). The rats were imaged at 7T at three timepoints for all animals: 3-5, 7-9, and 11-13 days after implantation. Whole-brain T1-weighted (before and after gadolinium contrast agent injection), diffusion, and fluid-attenuated inversion recovery scans were performed. In addition, single-slice saturation-transfer-weighted chemical exchange saturation transfer (CEST), magnetization transfer (MT), and water saturation shift referencing (WASSR) contrast Z-spectra and T1 and T2 maps were also acquired. The MT and WASSR Z-spectra and T1 map were fitted to a two-pool quantitative MT model to estimate the T2 of the free and macromolecular-bound water molecules, the relative macromolecular pool size (M0, MT), and the magnetization exchange rate from the macromolecular pool to the free pool (RMT). The T1-corrected apparent exchange-dependent relaxation (AREX) metric to isolate the CEST contributions was also calculated. The lesion on M0, MT and AREX maps with a B1 of 2μT best matched the hyperintensity on the post-contrast T1-weighted image. There was also good separation in Z-spectra between the lesion and contralateral cortex in the 2-μT CEST and 3- and 5-μT MT Z-spectra at all time points. A pairwise Wilcoxon signed-rank tests with Holm-Bonferroni adjustment on MRI parameters was performed and the differences between enhancing lesion and contralateral cortex for the MT ratio with 2μT saturation at 3.6ppm frequency offset (corresponding to the amide chemical group) and M0, MT were both strongly significant (p< 0.001) at all time points. This work has identified that differences between enhancing lesion and contralateral cortex are strongest in MTR with B1=2μT at 3.6ppm and relative macromolecular pool size (M0, MT) images over entire period of 3-13 days after cancer cell implantation.