Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Rodent models”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23Linked to original sources
PubMed2004

Ropinirole versus L-DOPA effects on striatal opioid peptide precursors in a rodent model of Parkinson's disease: implications for dyskinesia.

The dopamine precursor, L-3,4-dihydroxyphenylalanine (L-DOPA), remains the most common treatment for Parkinson's disease. However, following long-term treatment, disabling side effects, particularly L-DOPA-induced dyskinesias, are encountered. Conversely, D2/D3 dopamine receptor agonists, such as ropinirole, exert an anti-parkinsonian effect while eliciting less dyskinesia when administered de novo in Parkinson's disease patients. Parkinson's disease and L-DOPA-induced dyskinesia are both associated with changes in mRNA and peptide levels of the opioid peptide precursors preproenkephalin-A (PPE-A) and preproenkephalin-B (PPE-B). Furthermore, a potential role of abnormal opioid peptide transmission in dyskinesia is suggested due to the ability of opioid receptor antagonists to reduce the L-DOPA-induced dyskinesia in animal models of Parkinson's disease. In this study, the behavioural response, striatal topography and levels of expression of the opioid peptide precursors PPE-A and PPE-B were assessed, following repeated vehicle, ropinirole, or L-DOPA administration in the 6-OHDA-lesioned rat model of Parkinson's disease. While repeated administration of L-DOPA significantly elevated PPE-B mRNA levels (313% cf. vehicle, 6-OHDA-lesioned rostral striatum; 189% cf. vehicle, 6-OHDA-lesioned caudal striatum) in the unilaterally 6-OHDA-lesioned rat model of Parkinson's disease, ropinirole did not. These data and previous studies suggest the involvement of enhanced opioid transmission in L-DOPA-induced dyskinesia and that part of the reason why D2/D3 dopamine receptor agonists have a reduced propensity to elicit dyskinesia may reside in their reduced ability to elevate opioid transmission.

Animals↗
PubMed2004

Neuroprotective effect of rasagiline in a rodent model of Parkinson's disease.

Sprague-Dawley rats received a unilateral injection of 6-hydroxydopamine (6-OHDA) into the striatum and were treated daily for 6 weeks with increasing doses of monoamine oxidase type B inhibitor rasagiline [R(+)-N-propargyl-1-aminoindane] or saline (controls). Both doses of rasagiline markedly increased the survival of dopaminergic neurons in the lesioned substantia nigra, compared to controls (+97% and +119%, respectively). Treatment with the lower dose of rasagiline also abolished the motor stereotypies associated with nigrostriatal lesion. Our study supports the neuroprotective potential of chronic rasagiline administration in an experimental model of Parkinson's disease (PD).

Animals↗
PubMed2006

Transplanted adult neural progenitor cells survive, differentiate and reduce motor function impairment in a rodent model of Huntington's disease.

The present study investigated the ability for adult rat neural progenitor cells to survive transplantation, structurally repopulate the striatum and improve motor function in the quinolinic acid (QA) lesion rat model of Huntington's disease. Neural progenitor cells were isolated from the subventricular zone of adult Wistar rats, propagated in culture and labeled with BrdU (50 microM). Fourteen days following QA lesioning, one group of rats (n = 12) received a unilateral injection of adult neural progenitor cells ( approximately 180,000 cells total) in the lesioned striatum, while a second group of rats (n = 10) received a unilateral injection of vehicle only (sham transplant). At the time of transplantation adult neural progenitor cells were phenotypically immature, as demonstrated by SOX2 immunocytochemistry. Eight weeks following transplantation, approximately 12% of BrdU-labeled cells had survived and migrated extensively throughout the lesioned striatum. Double-label immunocytochemical analysis demonstrated that transplanted BrdU-labeled progenitor cells differentiated into either astrocytes, as visualized by GFAP immunocytochemistry, or mature neurons, demonstrated with NeuN. A proportion of BrdU-labeled cells also expressed DARPP-32 and GAD67, specific markers for striatal medium spiny projection neurons and interneurons. Rats transplanted with adult neural progenitor cells also demonstrated a significant reduction in motor function impairment as determined by apomorphine-induced rotational asymmetry and spontaneous exploratory forelimb use when compared to sham transplanted animals. These results demonstrate that adult neural progenitor cells survive transplantation, undergo neuronal differentiation with a proportion of newly generated cells expressing markers characteristic of striatal neurons and reduce functional impairment in the QA lesion model of Huntington's disease.

Analysis of Variance↗
PubMed2004

The physiological and pathophysiological roles of the GH/IGF-axis in the kidney: lessons from experimental rodent models.

The growth hormone (GH)/insulin-like growth factor (IGF) system plays an important role in renal development, growth, function and pathophysiology. IGF-I has been associated with renal/glomerular hypertrophy and compensatory renal growth. Potential effects on glomerular size are of interest, since an increase in glomerular size may be permissive for the development of glomerulosclerosis. In an effort to abolish the decline of renal function and possibly to restore the renal structure, different approaches have been tested in experimental models of nephropathy, focusing mainly on early renal changes. The involvement of the GH/IGF system in renal pathophysiology has been studied in much detail in the rat. In view of the growing interest in murine physiology, occurring in large part by genetically modified animals, this review examines those aspects of GH, IGFs, their receptors and binding proteins that relate both to mouse kidney physiology and to a number of conditions characterized by pathophysiological renal changes. A deeper understanding of the role of the GH/IGF system in renal dysfunction may stimulate the development of novel therapeutic approaches aiming at preventing or retarding various kidney diseases.

Animals↗
PubMed2003

Changes of mGluR4 and the effects of its specific agonist L-AP4 in a rodent model of diffuse brain injury.

OBJECTIVE: Excessive release of glutamate from nerve terminals following diffuse brain injury (DBI) is thought to contribute to neuronal calcium overload leading to calcium-mediated cell damage. Metabotropic glutamate receptor subtype 4 (mGluR4) is regarded as one of the neuroprotective receptors in mammalian brains. Therefore, the mGluR4 specific agonists might exert neuroprotective effects after DBI. The focus of this study is to examine the changes of expression of mGluR4 after DBI and the role of its specific agonist L-AP4 in vivo. METHODS: One hundred and sixty-one male SD rats were randomized into two groups. Group A included normal control, sham-operated control and DBI group. DBI was produced by Marmarou's diffuse head injury model. The mRNA expression of mGluR4 was detected by hybridization in situ. Group B included DBI alone, DBI treated with normal saline and DBI treated with L-AP4. All DBI rats were trained in a series of performance tests, following which they were subjected to DBI. At 1 and 12 h, animals were injected intracerebroventricularly with L-AP4 (100 mM, 10 microl) or normal saline, respectively. The rats were tested for motor and cognitive performance at 1, 3, 7, 14 days post-injury and the damaged neurons were detected. RESULTS: There was no significant difference between the normal control group and sham-operated group in the expression of mGluR4 (P>0.05). The animals exposed to DBI showed a significant increased expression of mRNA of mGluR4 compared with that of the sham-operated animals 1 h after injuries (P<0.05). At 6 h, the evolution of neuronal expression of mGluR4 in the trauma alone group was relatively static. Compared with saline-treated control animals, rats treated with L-AP4 showed decreased number of damaged neurons and a better motor and cognitive performance. CONCLUSIONS: The increased expression of mGluR4 is an important process in the pathophysiological of DBI and its specific agonist L-AP4 can provide a remarkable neuroprotection against DBI not only at the histopathological level but also in the motor and cognitive performance.

Aminobutyrates↗
PubMed2004

A polymeric membrane dressing with antinociceptive properties: analysis with a rodent model of stab wound secondary hyperalgesia.

UNLABELLED: The putative antinociceptive properties of a commercially available polymeric membrane dressing were tested by using a hind limb penetrating stab wound model in which secondary hyperalgesia could be evaluated from the hind paw. We examined the responses to mechanical and thermal stimuli applied to the hind paw remote to 2 small penetrating stab wounds of the calf. Application of the polymeric membrane dressing, but not gauze dressing, significantly reduced the development of both mechanical and thermal hyperalgesia induced by the penetrating stab wounds. In addition, animals with stab wounds showed a significant decrease in cage activity, and this decrease was prevented by application of the polymeric dressing. Analysis of spinal cord Fos expression demonstrated that the polymeric membrane, but not gauze, dressing significantly decreased stab wound-induced Fos expression in laminae I to VI of the ipsilateral L3-L5 cord segments. In addition, application of the polymeric membrane, but not gauze, dressing to the hind limb of naïve animals elicited Fos expression in laminae III and IV of the lumbar spinal cord. The data indicate that this model might be useful for evaluation of the mechanisms underlying deep tissue injury-induced secondary hyperalgesia, but they also demonstrate that the polymeric membrane dressing tested is capable of significantly reducing secondary hyperalgesia. PERSPECTIVE: Surgery and other types of penetrating wounds cause pain that is not always relieved by opioids and/or less potent analgesics. The present results suggest that the polymeric membrane dressing tested here may be used alone or in conjunction with analgesics to relieve pain caused by penetrating tissue injury.

Administration, Topical↗
PubMed2005

Gubernacular cell division in different rodent models of cryptorchidism supports indirect androgenic action via the genitofemoral nerve.

PURPOSE: The role of the "gubernaculum" in testicular descent remains controversial. Androgens are proposed to act indirectly by the genitofemoral nerve (GFN) releasing calcitonin gene-related peptide. The authors studied the effects of sensory nerve ablation and androgen blockade on mitosis in the gubernacular tip to determine whether androgens act directly or indirectly. METHODS: Five rat models were examined for bromodeoxyuridine (BUdR)-labeling: (i) Sprague-Dawley (SD) rats (controls), (ii) prenatal flutamide-treated rats (75 mg/kg to dams on D16-19 gestation), (iii) neonatal capsaicin-treated rats (50 mg/kg, subcutaneous on day 0), (iv) congenitally cryptorchid transcrotal (TS) rats, and (v) capsaicin-treated TS rats (50 mg/kg, subcutaneous on day 0). Newborn rats were collected at days 0, 2, 4, 6, 8, and 10 (age, n = 5/model, n = 30) and were injected intraperitoneally with 1 mg/kg BUdR, 2 hours before killing. Histological sections of gubernaculum were examined immunohistochemically for BUdR labeling. RESULTS: In SD (control) rats, DNA synthesis in the gubernacular tip was high at birth, reached a peak at day 2, and then decreased progressively until day 10. A similar pattern was observed in TS rats. However, quantitatively, the levels were significantly higher. In flutamide-treated rats, DNA synthesis was suppressed until day 6, similar suppression was observed in capsaicin-treated SD, and TS rats until day 4. CONCLUSIONS: Flutamide, a competitive androgen receptor blocker, reduces gubernacular mitosis to basal levels until day 6, highlighting the importance of androgen receptor. Excess DNA accumulation in TS rats is consistent with the known excess of GFN fibers and calcitonin gene-related peptide in this mutant. Capsaicin-inhibited mitosis in both day 2 SD and TS rats suggests that the GFN mediates androgen action on early postnatal gubernacular DNA synthesis and growth.

Analysis of Variance↗
PubMed2006

Isolated perfusion of a tubed superficial epigastric flap in a rodent model.

BACKGROUND: Isolated perfusion models can yield important data regarding metabolism of the skin. An effective model must remain stable during perfusion but respond appropriately to metabolic and vascular stimuli. We describe the design and characterization of a tubed superficial epigastric isolated perfusion flap. MATERIALS AND METHODS: Tubed superficial epigastric flaps were created in 20 male Sprague Dawley rats. Forty-eight hours later the femoral vessels were cannulated and the flaps were perfused using a Krebs-Heinseleit buffer containing albumin for a period of 2 h. In five of the flaps norepinephrine and acetylcholine were added sequentially to the perfusate to determine vascular reactivity. In a further four flaps insulin (20 U/liter) and iodoacetate (5 mM) were added to the perfusate to confirm that the flap was metabolically active and reactive. Venous outflow was collected at regular intervals and analyzed for electrolytes, lactate, and glucose content. Vascularity and skin perfusion were characterized using barium microangiography and methylene blue dye injection. RESULTS: This flap model was found to be stable in terms of arterial pressure, electrolyte levels, and lactate production over the perfusion period. Norepinephrine caused a sharp increase in vascular resistance, which was reversed by administration of acetylcholine. Lactate production increased appropriately with the addition of insulin to the perfusate with a rapid decline following addition of the glycolysis inhibitor iodoacetate. There was no leakage of perfusate or significant swelling of the flap during the perfusion. CONCLUSIONS: The tubed superficial epigastric artery flap makes an effective model for isolated perfusion studies of the skin with a wide range of experimental applications.

Acetylcholine↗
PubMed2004

Gene expression patterns associated with infertility in humans and rodent models.

Modern genomic technologies such as DNA arrays provide the means to investigate molecular interactions at an unprecedented level, and arrays have been used to carry out gene expression profiling as a means of identifying candidate genes involved in molecular mechanisms underlying a variety of phenotypes. By comparing gene expression profiles from normal and abnormal human testes with those from comparable infertile mouse models, we endeavored to identify genes and gene networks critical for male fertility. We used commercially available filter-based DNA arrays to analyze testicular gene expression from eight human testis biopsies and three different infertile mouse models (atrichosis mutation, ataxia telangiectasia knockout and CREMtau knockout). Forty-seven mouse genes exhibited differential testicular gene expression (P <0.01) associated with male infertility. These included genes involved in DNA repair (Vim, Rad23A, Rad23B), glutathione metabolism (Gsr, Gstp 1, Mgst1), proteolysis (Ace, Casp1, Ctsd), spermatogenesis (Prlr, Tmsb4 and Zfp-37) and stress response (Hsp 1, Osp94). The expression of 19 human genes was different (P<0.05) between normal and abnormal samples, including those associated with apoptosis (GADD45), gonad development (SOX9), proteolysis (PSMC3, SPINK2, TIMP3, UBE213) and signal transduction (DLK1, NAP4, S100A10). Direct comparison of differentially expressed human and mouse genes identified glucose phosphate isomerase, and the highly similar human tissue inhibitor of metalloproteinase 3 (TIMP3) and mouse Timp2. Using DNA microarrays to profile gene expression in testes from infertile animal models and humans will be useful for understanding congenital infertility, and also infertility caused by environmental exposures where the same genes and molecular mechanisms are involved.

Animals↗
PubMed2005

Prolonged blockade of NMDA or mGluR5 glutamate receptors reduces nigrostriatal degeneration while inducing selective metabolic changes in the basal ganglia circuitry in a rodent model of Parkinson's disease.

We compared the neuroprotective and metabolic effects of chronic treatment with ionotropic or metabotropic glutamate receptor antagonists, in rats bearing a unilateral nigrostriatal lesion induced by 6-hydroxydopamine (6-OHDA). The ionotropic, N-methyl-D-aspartate receptor antagonist MK-801 increased cell survival in the substantia nigra pars compacta (SNc) and corrected the metabolic hyperactivity (increased cytochrome oxidase activity) of the ipsilateral substantia nigra pars reticulata (SNr) associated with the lesion, but showed no effects on the 6-OHDA-induced hyperactivity of the subthalamic nucleus (STN). Significant-although less pronounced-protection of SNc neurons was also observed following treatment with the metabotropic glutamate receptor (mGluR5) antagonist 2-methyl-6-(phenylehtynyl)-pyridine (MPEP). As opposed to MK-801, MPEP abolished the STN metabolic hyperactivity associated with the nigrostriatal lesion, without affecting SNr activity. Specific modulation of STN hyperactivity obtained with mGluR5 blockade may, therefore, open interesting perspectives for the use of this class of compounds in the treatment of Parkinson's disease.

Animals↗
PubMed2006

Myostatin inhibition slows muscle atrophy in rodent models of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease leading to motor neuron cell death, but recent studies suggest that non-neuronal cells may contribute to the pathological mechanisms involved. Myostatin is a negative regulator of muscle growth whose function can be inhibited using neutralizing antibodies. In this study, we used transgenic mouse and rat models of ALS to test whether treatment with anti-myostatin antibody slows muscle atrophy, motor neuron loss, or disease onset and progression. Significant increases in muscle mass and strength were observed in myostatin-antibody-treated SOD1(G93A) mice and rats prior to disease onset and during early-stage disease. By late stage disease, only diaphragm muscle remained significantly different in treated animals in comparison to untreated controls. Myostatin inhibition did not delay disease onset nor extend survival in either the SOD1(G93A) mouse or rat. Together, these results indicate that inhibition of myostatin does not protect against the onset and progression of motor neuron degenerative disease. However, the preservation of skeletal muscle during early-stage disease and improved diaphragm morphology and function maintained through late stage disease suggest that anti-myostatin therapy may promote some improved muscle function in ALS.

Age of Onset↗
PubMed2005

A serotonin 5-HT1A receptor agonist prevents behavioral sensitization to L-DOPA in a rodent model of Parkinson's disease.

Marked fluctuation of dopamine concentration in the striatum following long-term L-DOPA administration contributes to the development of L-DOPA-induced motor complications including L-DOPA-induced dyskinesias and wearing-off in patients with Parkinson's disease. We have shown that pretreatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A (5-hydroxytryptamine) receptor agonist, alleviates fluctuation of dopamine levels in the dopamine-denervated striatum of 6-hydroxydopamine-lesioned (hemiparkinsonian) rats after L-DOPA treatment. To determine whether co-administration of 8-OH-DPAT with L-DOPA prevents L-DOPA-induced motor complications, we examined rotation behavior and levels of messenger RNAs coding for dynorphin and glutamic acid decarboxylase in the striatum of 6-hydroxydopamine-lesioned rats treated with L-DOPA alone or L-DOPA + 8-OH-DPAT, twice daily, for 2 weeks. Co-administration of 8-OH-DPAT inhibited an increase of rotation behavior to L-DOPA and L-DOPA-induced increases in levels of messenger RNAs coding for dynorphin and glutamic acid decarboxylase in the dopamine-denervated striatum, both of which are established indices of L-DOPA-induced motor complications. These results suggest that pharmaceutical products that stimulate 5-HT1A receptors could prove useful in prevention of the development of L-DOPA-induced motor complications in patients with Parkinson's disease.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2006

Beneficial effects of fruit extracts on neuronal function and behavior in a rodent model of accelerated aging.

Exposing young rats to particles of high-energy and charge (HZE particles) enhances indices of oxidative stress and inflammation and disrupts the functioning of the dopaminergic system and behaviors mediated by this system in a manner similar to that seen in aged animals. Previous research has shown that diets supplemented with 2% blueberry or strawberry extracts have the ability to retard and even reverse age-related deficits in behavior and signal transduction in rats, perhaps due to their antioxidant and anti-inflammatory properties. This study evaluated the efficacy of these diets on irradiation-induced deficits in these parameters by maintaining rats on these diets or a control diet for 8 weeks prior to being exposed to whole-body irradiation with 1.5 Gy of 1 GeV/n high-energy (56)Fe particles. Irradiation impaired performance in the Morris water maze and measures of dopamine release 1 month following radiation; these deficits were protected by the antioxidant diets. The strawberry diet offered better protection against spatial deficits in the maze because strawberry-fed animals were better able to retain place information (a hippocampally mediated behavior) compared to controls. The blueberry diet, on the other hand, seemed to improve reversal learning, a behavior more dependent on intact striatal function. These data suggest that (56)Fe particle irradiation causes deficits in behavior and signaling in rats which were ameliorated by an antioxidant diet and that the polyphenols in these fruits might be acting in different brain regions.

Aging↗
PubMed2004

Adenosine A(2A) receptor-mediated modulation of GABA and glutamate release in the output regions of the basal ganglia in a rodent model of Parkinson's disease.

A target neuron of adenosine A(2A) receptor antagonists to exert anti-parkinsonian activities has been currently identified to be, at least in part, striatopallidal medium spiny neurons (MSNs). In the present study, we determine whether A(2A) receptor-mediated modulation is associated with changes in the release of GABA and glutamate in the substantia nigra pars reticulata (SNr), an output structure of the whole basal ganglia network, using in vivo microdialysis in a rat Parkinson's disease (PD) model. In 6-hydroxydopamine (OHDA)-lesioned rats compared with normal rats, basal extracellular GABA levels in the SNr show no change, whereas basal glutamate levels are significantly increased. Oral administration of the A(2A) receptor-selective antagonist (E-1,3-diethyl-8-(3,4-dimethoxystyryl)-7-methyl-3,7-dihydro-1-H-purine-2,6-dion (KW-6002) to 6-OHDA-lesioned rats at 1 mg/kg caused a marked and sustained increase of GABA and glutamate levels in the SNr. The increase of nigral glutamate by KW-6002 was abolished by a kainic acid-induced lesion of the globus pallidus (GP) or subthalamic nucleus (STN) in 6-OHDA-lesioned rats, whereas the increase of nigral GABA was completely blocked by the GP-lesion but only partially blocked by the STN-lesion. These results indicate that changes in neurotransmitter release in the SNr brought about by KW-6002 are largely attributable to blockade of A(2A) receptor-mediated modulation of striatopallidal MSNs. Thus, these actions of KW-6002 on striatopallidal MSNs may be the main mechanism for ameliorating PD by A(2A) antagonists.

Adenosine A2 Receptor Antagonists↗
PubMed2004

Effects of sensorimotor restriction and anoxia on gait and motor cortex organization: implications for a rodent model of cerebral palsy.

Chronic or acute perinatal asphyxia (PA) has been correlated with the subsequent development of cerebral palsy (CP), a developmental neurological disorder characterized by spasticity and motor abnormalities often associated with cognitive deficits. Despite the prevalence of CP, an animal model that mimics the lifetime hypertonic motor deficits is still not available. In the present study, the consequences of PA on motor behavior, gait and organization of the primary motor cortex were examined in rats, and compared with the behavioral and neurological consequences of early postnatal movement-restriction with or without oxygen deprivation. Rats subjected to PA had mild increases in muscular tone accompanied by subtle differences in walking patterns, paralleled by significantly altered but relatively modest disorganization of their primary motor cortices. Movement-restricted rats, suffering PA or not, had reduced body growth rate, markedly increased muscular tone at rest and with active flexion and extension around movement-restricted joints that resulted in abnormal walking patterns and in a profoundly distorted representation of the hind limbs in the primary motor cortex. Within the sensorimotor-restricted groups, non-anoxic rats presented the most abnormal pattern and the greatest cortical representational degradation. This outcome further supports the argument that PA per se may represent a substrate for subtle altered motor behaviors, and that PA alone is sufficient to alter the organization of the primary motor cortex. At the same time, they also show that early experience-dependent movements play a crucial role in shaping normal behavioral motor abilities, and can make a powerful contribution to the genesis of aberrant movement abilities.

Animals↗
PubMed2005

Training specificity, graft development and graft-mediated functional recovery in a rodent model of Huntington's disease.

Neuronal function and morphology are affected by the environment and the behavioral experience. Here we report on the effects of differential training protocols on the development and the functional recovery mediated by intrastriatal striatal grafts. Rats were trained exclusively on the left or the right paw to perform on the skilled staircase task before being lesioned unilaterally in the dorsal striatum with quinolinic acid. E15 whole ganglionic eminence suspension grafts were implanted into the lesioned striatum. Subsequent testing probed unilateral performance of the affected contralateral paw, as well as bilateral performance. The grafted animals were initially as impaired as the lesioned, but partially recovered their performance with additional training. Grafted animals with appropriate previous experience initially performed better on the staircase test, but the advantage was transient. Furthermore, the grafted animals performed better with their affected paw under forced choice than under conditions when both paws were simultaneously probed. Improvements of the grafted animals were also observed on tests of forelimb akinesia and asymmetry. Morphological data suggest that the training conditions influenced the development specifically of striatal-like, but not of non-striatal like, neurones within the grafts. The grafts were smaller containing less striatal-like neurones in animals that were trained on the contralateral side prior to lesioning and grafting. The results support the hypothesis that unilateral training sensitizes the striatum that subserves the motor learning, leading to exacerbated excitotoxic lesions and to an environment less conducive for graft development.

Animals↗
PubMed2006

Delayed minocycline treatment reduces long-term functional deficits and histological injury in a rodent model of focal ischemia.

The absence of effective treatments for stroke presents a critical need for novel strategies that can reduce ischemic injury. Neuroinflammation following focal ischemia induces secondary injury in the region surrounding the insult, thus anti-inflammatory agents are potential neuroprotectants. Minocycline is one such agent possessing neuroprotective properties, however many studies examining minocycline after ischemia have used minimal delays between ischemia and treatment, short survival periods, and lack measures of functional outcome. Such studies do not distinguish whether minocycline provides sustained protection or merely delays cell death. This study was designed to address some of these concerns. Male Sprague-Dawley rats were treated with multiple doses of minocycline (45 mg/kg i.p.) or vehicle beginning 2.5 h after endothelin-1-induced focal ischemia. Measures of forelimb asymmetry and skilled reaching (staircase test) were used to determine functional outcome 7, 15 and 28 days after ischemia. Long-term functional assessment indicates that minocycline provides limited benefit in the staircase test, but confers long-term benefit in the forelimb asymmetry test. Subcortical and whole hemisphere infarct volumes were reduced by 41 and 39% respectively in minocycline-treated animals. Further analysis revealed that minocycline attenuated long-term white matter damage adjacent to the striatal injury core, which correlated with sustained functional benefits. This study indicates that delayed minocycline treatment improves long-term functional outcome which is linked to protection of both white and gray matter.

Analysis of Variance↗