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Biochemical and morphological validation of a rodent model of organophosphorus-induced delayed neuropathy.

Exposure to certain organophosphates (OPs) produces a delayed degeneration of the longest and largest nerve fibers (OPIDN). Until recently, investigators have used the chicken as the primary experimental model of OPIDN. Although the chicken is extremely sensitive to the ataxia associated with this neuropathy, it lacks an extensive biochemical, electrophysiological and pathological data-base. Because of this we set out to develop a rodent model of OPIDN with morphological and biochemical correlates similar to those seen in the chicken. Historically the rat had been labeled insensitive to OPIDN because of its lack of demonstrable ataxia in response to the neuropathic OPs. This paper describes the validation of a rodent model with biochemical and morphological endpoints similar to those described in the clinical and experimental literature for other models of OPIDN.

Animals↗

Grafts of EGF-responsive neural stem cells derived from GFAP-hNGF transgenic mice: trophic and tropic effects in a rodent model of Huntington's disease.

The present study examined whether implants of epidermal growth factor (EGF)-responsive stems cells derived from transgenic mice in which the glial fibrillary acid protein (GFAP) promoter directs the expression of human nerve growth factor (hNGF) could prevent the degeneration of striatal neurons in a rodent model of Huntington's disease (HD). Rats received intrastriatal transplants of GFAP-hNGF stem cells or control stem cells followed 9 days later by an intrastriatal injection of quinolinic acid (QA). Nissl stains revealed large striatal lesions in rats receiving control grafts, which, on average, encompassed 12.78 mm3. The size of the lesion was significantly reduced (1.92 mm3) in rats receiving lesions and GFAP-hNGF transplants. Rats receiving QA lesions and GFAP-hNGF-secreting grafts stem cell grafts displayed a sparing of striatal neurons immunoreactive (ir) for glutamic acid decarboxylase, choline acetyltransferase, and neurons histochemically positive for nicotinamide adenosine diphosphate. Intrastriatal GFAP-hNGF-secreting implants also induced a robust sprouting of cholinergic fibers from subjacent basal forebrain neurons. The lesioned striatum in control-grafted animals displayed numerous p75 neurotrophin-ir (p75NTR) astrocytes, which enveloped host vasculature. In rats receiving GFAP-hNGF-secreting stem cell grafts, the astroglial staining pattern was absent. By using a mouse-specific probe, stem cells were identified in all animals. These data indicate that cellular delivery of hNGF by genetic modification of stem cells can prevent the degeneration of vulnerable striatal neural populations, including those destined to die in a rodent model of HD, and supports the emerging concept that this technology may be a valuable therapeutic strategy for patients suffering from this disease.

Animals↗

Metabolic effects of thioctic acid in rodent models of insulin resistance and diabetes.

1. The antioxidant thioctic acid (TA) has been used in the treatment of diabetic neuropathy and recent studies have suggested that TA also has pancreatic and peripheral effects that improve glucose transport and metabolism. In the present study, the metabolic effects of TA were evaluated in rodent models of insulin resistance (fructose-fed Sprague-Dawley rat) and insulin deficiency (streptozotocin (STZ)-induced diabetic rat). Oral and intravenous glucose tolerance tests (OGTT and IVGTT, respectively) were performed in conscious rats after treatment with 50 mg/kg per day TA or vehicle for 5 days. 2. Fructose feeding for 7 days induced insulin resistance and impaired glucose tolerance and hypertriglycerideaemia. Treatment of fructose-fed rats with TA had no significant effect on fasting or stimulated glucose levels or on fasting triglyceride concentrations (e.g. the area under the curve for glucose (AUCglu) following OGTT was 1233 +/- 67 and 1284 +/- 59 in fructose-fed rats treated with either TA (n = 12) or vehicle (n = 12), respectively). Similarly, TA had no significant effect on IVGTT profiles in fructose-induced insulin resistance. 3. Low-dose STZ (80 mg/kg, i.p., over 2 days) induced hyperglycaemia, but TA had no significant glucose-lowering effects in STZ-diabetic rats (AUCglu (OGTT) following oral administration was 5507 +/- 27 and 5450 +/- 27 in TA (n = 12) and vehicle-treated (n = 12) rats, respectively). Nor did pretreatment with TA affect the diabetogenic response to STZ. 4. In contrast with previous in vitro studies reporting favourable metabolic effects of TA, the present study shows that after short-term oral therapy there are no significant improvements in glucose tolerance in rodent models of insulin resistance and insulin deficiency. Thioctic acid is unlikely to be of therapeutic benefit as an anti-diabetic drug in clinical practice.

Animals↗

Neuroprotective actions of the ginseng extract G115 in two rodent models of Parkinson's disease.

The herbal remedy, ginseng, has recently been demonstrated to possess neurotrophic and neuroprotective properties, which may be useful in preventing various forms of neuronal cell loss including the nigrostriatal degeneration seen in Parkinson's disease (PD). In these studies, we examine the potential neuroprotective actions of the ginseng extract, G115, in two rodent models of PD. Animals received oral administration of G115 prior to and/or following exposure to the parkinsonism-inducing neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), in mice, or its toxic metabolite, 1-methyl-4-phenylpyridinium (MPP(+)), in rats. Such treatment significantly and dramatically blocked tyrosine hydroxylase-positive cell loss in the substantia nigra and reduced the appearance of locomotor dysfunction. Thus, oral administration of ginseng appears to provide protection against neurotoxicity in rodent models of PD. Further examination of the neuroprotective actions of ginseng and its various elements may provide a potential means of slowing the progress of PD.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Erythropoietin and GDNF enhance ventral mesencephalic fiber outgrowth and capillary proliferation following neural transplantation in a rodent model of Parkinson's disease.

Low dopaminergic cell survival and suboptimal fiber reinnervation are likely major contributing factors for the limited benefits of neural transplantation in Parkinson's disease (PD) patients. Glial cell lined-derived neurotrophic factor (GDNF) has been shown to enhance dopaminergic cell survival and fiber outgrowth of the graft site as well as promote behavioral recovery in rodent models of PD, while erythropoietin (EPO) can produce dopaminergic neuroprotective effects against 6-hydroxydopamine (6-OHDA) exposure on cultured neurons and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice. The aim of this study was to determine if fetal ventral mesencephalic (FVM) tissue exposed to hibernation media containing a combination of GDNF and EPO could enhance dopaminergic graft survival, striatal reinnervation and functional recovery in a 6-OHDA rodent model of PD. FVM tissue was dissected from 14-day-old rat fetuses and placed for 6 days in hibernation media alone, and in hibernation media that received either a daily administration of GDNF, EPO or a combination of GDNF and EPO. Following hibernation, FVM cells were transplanted as a single cell suspension into the striatum of unilateral 6-OHDA-lesioned rats. Rotational behavioral assessment revealed animals that received FVM tissue exposed to GDNF, EPO or the combination of both drugs had accelerated functional recovery. Immunohistochemical and stereological assessment revealed a significant increase in graft fiber density and angiogenesis into the graft when compared with control. These findings suggest that the hibernation of FVM tissue in a combination of GDNF and EPO can enhance graft efficacy and may have important implications for tissue preparation protocols for clinical neural transplantation in PD.

Animals↗

Understanding the Pathogenesis of Inflammation Using Rodent Models: Identification of a Transcription Factor (NFkappaB) Necessary for Development of Inflammatory Injury.

The acute inflammatory response is composed of a complex cascade of mediators, which facilitate the removal of infectious agents and restore normal tissue function. Experiments using cultured cells have demonstrated that the transcription factor nuclear factor kappa B (NFkappaB) is critically important for the expression of numerous proinflammatory mediators. However, extrapolation of data derived from these types of studies often does not represent the in vivo response accurately. Application of rodent models of inflammation has allowed detailed study of the role of NFkappaB and its transcriptional products in a variety of inflammatory diseases. This article reviews the importance of rodent models for the study of complex biological systems, such as acute inflammation, and presents ways in which these models have been used to characterize the requisite function of NFkappaB in these responses.

Journal Article↗

Role of astrocytic S100beta in behavioral hypersensitivity in rodent models of neuropathic pain.

S100beta is a calcium-binding peptide produced mainly by astrocytes that exerts paracrine and autocrine effects on neurons and glia. We have previously shown that S100beta is markedly elevated at the mRNA level in the spinal cord following peripheral inflammation, intraplantar administration of complete Freund's adjuvant in the rat. The purpose of the present study was to further investigate the role of astrocytic S100beta in mediating behavioral hypersensitivity in rodent models of persistent pain. First, we assessed the lumbar spinal cord expression of S100beta at the mRNA and protein level using real-time RT-PCR, Western blot and immunohistochemistry analysis following L5 spinal nerve transection in rats, a rodent model of neuropathic pain. Second, we assessed behavioral hypersensitivity (mechanical allodynia) in wild type and genetically modified mice lacking or overexpressing S100beta following L5 spinal nerve transection. Third, we assessed the expression level of S100beta protein in the CD1 wild type mice after nerve injury. We report that lumbar spinal S100beta mRNA steadily increased from days 4-28 after nerve injury. S100beta protein in the lumbar spinal cord was significantly increased in both rats and mice at day 14 following nerve injury as compared with sham control groups. S100beta genetically deficient mice displayed significantly increased tactile thresholds (reduced response to non-noxious stimuli) after nerve injury as compared with the wild type group. S100beta overexpressing mice displayed significantly decreased tactile threshold responses (enhanced response to non-noxious stimuli). Together, these results from both series of experiments using a peripheral nerve injury model in two different species implicate the involvement of glial-derived S100beta in the pathophysiology of neuropathic pain.

Animals↗

Neuropeptides and the social brain: potential rodent models of autism.

Conducting basic scientific research on a complex psychiatric disorder, such as autism, is a challenging prospect. It is difficult to dissociate the fundamental neurological and psychological processes that are disturbed in autism and, therefore, it is a challenge to discover accurate and reliable animal models of the disease. Because of their role in animal models of social processing and social bonding, the neuropeptides oxytocin and vasopressin are strong candidates for dysregulation in autism. In this review, we discuss the current animal models which have investigated oxytocin and vasopressin systems in the brain and their effects on social behavior. For example, mice lacking the oxytocin gene have profound deficits in social processing and social recognition, as do rats lacking vasopressin or mice lacking the vasopressin V1a receptor (V1aR). In another rodent model, monogamous prairie voles are highly social and form strong pair bonds with their mates. Pair bonds can be facilitated or disrupted by perturbing the oxytocin and vasopressin systems. Non-monogamous vole species that do not pair bond have different oxytocin and V1aR distribution patterns in the brain than monogamous vole species. Potential ties from these rodent models to the human autistic condition are then discussed. Given the hallmark disturbances in social function, the study of animal models of social behavior may provide novel therapeutic targets for the treatment of autism.

Animals↗

Zwitterionic phospholipids enhance aspirin's therapeutic activity, as demonstrated in rodent model systems.

We have recently reported that the Gl toxicity of aspirin is markedly reduced when the drug is preassociated with the zwitterionic phospholipid dipalmitoylphosphatidycholine (DPPC) before intragastric administration. The present study was designed to determine whether the biological availability and therapeutic activity of aspirin were affected by chemically associating the drug with DPPC. To evaluate this, we compared the kinetics of entry of labeled aspirin into the blood, after intragastric administration of the drug in the free and lipid-associated states; we also tested the ability of the above formulations to inhibit fever, inflammation and pain in appropriate rodent model systems. We found that although the Gl absorption of free aspirin and that of the aspirin/DPPC complex were similar, in all three rodent models the complex had significantly greater antipyretic, anti-inflammatory and analgesic efficacy than aspirin alone. Dose-response analyses employing the fever model demonstrated that potency of aspirin to reduce fever was increased 5 to 10-fold when the aspirin was intragastrically administered in the lipid-associated state. We conclude that the therapeutic activity of aspirin to inhibit fever, inflammation and pain is remarkably enhanced when the drug is intragastrically administered in chemical association with the zwitterionic phospholipid DPPC. A number of molecular mechanisms have been proposed to explain the observed phospholipid-dependent increase in aspirin's therapeutic activity.

1,2-Dipalmitoylphosphatidylcholine↗

In contrast to AAV-mediated Cntf expression, AAV-mediated Gdnf expression enhances gene replacement therapy in rodent models of retinal degeneration.

While AAV- and lentivirus-mediated gene replacement therapy can produce structural and functional improvements in various animal models of inherited retinal degeneration, this approach often has very limited effects on the rate of photoreceptor cell loss. Neurotrophic factors such as ciliary neurotrophic factor (CNTF) and glial cell line-derived neurotrophic factor (GDNF) have been shown to prolong photoreceptor survival in rodent models of retinal degeneration, but AAV-mediated Cntf expression also results in suppression of electrophysiological responses from the retina. In this study using mice, we show that while the deleterious effects mediated by CNTF are dose-dependent, administering a dose of CNTF that does not adversely affect retinal function precludes its ability to delay photoreceptor cell death. In evaluating GDNF as a neuroprotective agent, we show that AAV-mediated Gdnf expression does not produce adverse effects similar to those of CNTF. In addition, we demonstrate the ability of AAV-mediated delivery of Gdnf to slow cell death in two rodent models of retinitis pigmentosa and to enhance retinal function in combination with the relevant gene replacement therapy. These data show for the first time that a combination of these approaches can provide enhanced rescue over gene replacement or growth factor therapy alone.

Animals↗

Exercise induces behavioral recovery and attenuates neurochemical deficits in rodent models of Parkinson's disease.

Exercise is thought to improve motor function and emotional well-being in patients with Parkinson's disease (PD). However, it is not clear if the improvements are due to neurochemical alterations within the affected nigrostriatal region or result from a more general effect of exercise on affect and motivation. In this study we show that motorized treadmill running improves the neurochemical and behavioral outcomes in two rodent models of PD: the unilateral 6-hydroxydopamine (6-OHDA) rat model and bilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model in aged C57bl mice. Exposure to the dopamine (DA) toxins 6-OHDA or MPTP resulted in permanent behavioral and neurochemical loss. In contrast, when lesioned animals were exposed to treadmill activity two times a day for the first 10 days post-lesion they displayed no behavioral deficits across testing days and had significant sparing of striatal DA, its metabolites, tyrosine hydroxylase, vesicular monoamine transporter, and DA transporter levels compared to lesion sedentary animals. These results demonstrate that exercise following nigrostriatal damage ameliorates related motor symptoms and neurochemical deficits in rodent models of PD.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

beta-cell stimulus - secretion coupling defects in rodent models of obesity.

Hyperinsulinemia accompanies obesity in human patients and experimental rodent models and exacerbates insulin resistance, but the causes of increased insulin secretion remain obscure. This review examines progress in defining biochemical and molecular beta-cell defects that have elucidated in the past 5 years. Some defects, such as decreased glucose transport, decreased mitochondrial FAD-linked glycerophosphate dehydrogenase activity, and altered anomeric specificity for glucose, become evident only after onset of non-insulin-dependent diabetes mellitus. Thus, these defects are unlikely to play a role in the pathogenesis of hyperinsulinemia in obesity. Other biochemical changes, including increased glucokinase and (or) hexokinase function, increased glucose cycling, and altered regulation of intracellular Ca2+ are present in obese nondiabetic animals and may therefore contribute to development of hyperinsulinemia. Few developmental studies have been performed to correlate onset of defects with environmentally and genetically mediated control mechanisms of beta-cell function. However, the availability of new molecular biology techniques should facilitate identification of factors causing hyperinsulinemia in obesity.

Animals↗

Effects of PYY[3-36] in rodent models of diabetes and obesity.

BACKGROUND: Peptide YY (PYY) is a 36 amino-acid peptide secreted from ileal L cells following meals. The cleaved subpeptide PYY[3-36] is biologically active and may constitute the majority of circulating PYY-like immunoreactivity. The peptide family that includes PYY, pancreatic peptide and neuropeptide Y is noted for its orexigenic effect following intracerebroventricular administration. OBJECTIVE: To investigate the effects of peripheral (intraperitoneal and chronic subcutaneous) infusions of PYY[3-36] on food intake, body weight and glycemic indices. DESIGN/RESULTS: Food intake was measured in normal mice and in several rodent models of obesity and type II diabetes. In marked contrast to the reported central orexigenic effects, in the present study, PYY[3-36] acutely inhibited food intake by up to 45%, with an ED(50) of 12.5 microg/kg in fasted female NIH/Swiss mice. A 4-week infusion reduced weight gain in female ob/ob mice, without affecting the cumulative food intake. In diet-induced obese male mice, PYY[3-36] infusion reduced cumulative food intake, weight gain and epididymal fat weight (as a fraction of carcass) with similar ED(50)'s (466, 297 and 201 microg/kg/day, respectively) and prevented a diet-induced increase in HbA1c. Infusion at 100 microg/kg/day for 8 weeks in male fa/fa rats reduced the weight gain (288+/-11 vs 326+/-12 g in saline-infused controls; P<0.05), similar to effects in a pair-fed group. In female ob/ob and db/db mice, there was no acute effect of PYY[3-36] on plasma glucose concentrations. In male diabetic fatty Zucker rats, PYY[3-36] infused for 4 weeks reduced HbA1c and fructosamine (ED(50)'s 30 and 44 microg/kg/day). CONCLUSION: Peripheral PYY[3-36] administration reduced the food intake, body weight gain and glycemic indices in diverse rodent models of metabolic disease of both sexes. These findings justify further exploration of the potential physiologic and therapeutic roles of PYY[3-36].

Animals↗

Reversal of a cholinergic-induced deficit in a rodent model of recognition memory by the selective 5-HT6 receptor antagonist, Ro 04-6790.

RATIONALE: Accumulating evidence suggests a potential role for the 5-HT(6 )receptor in cognitive function and the potential use of 5-HT(6) receptor antagonists in the treatment of learning and memory disorders. OBJECTIVES: The aim of the current study was to investigate the effect of the selective 5-HT(6) receptor antagonist, Ro 04-6790, on both the performance of normal adult rats and restoration of a pharmacological disruption of memory function produced by the non-selective muscarinic receptor antagonist, scopolamine, or the dopamine D(2) receptor antagonist, raclopride, in a rodent model of recognition memory. METHODS: Passive, perceptually based, recognition memory was assessed using a novel object discrimination task. Following habituation to an arena, rats were presented with two identical objects during trial 1 (T(1)) and a novel and familiar object during trial 2 (T(2)). The time spent exploring the two objects in each trial was measured and novel object discrimination assessed in T(2). RESULTS: In the absence of drug all rats spent an equal time exploring the two identical objects in T(1) but more time exploring the novel object in T(2). Scopolamine (but not N-methylscopolamine) and raclopride both produced a dose-dependent reduction in novel object discrimination whilst the 5-HT(6) receptor antagonist, Ro 04-6790, had no effect on discrimination when given alone but completely reversed the scopolamine- but not the raclopride-induced deficit. CONCLUSION: This study demonstrates that acute administration of Ro 04-6790 reverses a cholinergic but not a dopaminergic deficit in a rodent model of recognition memory and provides further support for a role of the 5-HT(6) receptor in the regulation of cognitive function.

Animals↗

Intramedullary osseointegration: development of a rodent model and study of histology and neuropeptide changes around titanium implants.

A rodent model has been developed to explore intramedullary osseointegration and the phenomena of osseoperception. Osseointegration with endosseous titanium implants is frequently used in oral surgery. More recently, intramedullary osseointegration has been used for direct skeletal anchoring of amputation prostheses, a procedure that provides for a stable prosthesis with improved perception. Experimental, commercially pure titanium rods with threaded ends were surgically implanted in the intramedullary space of 18 rat femurs, and were left in place for 8 wk. Microscopic and immunohistochemical observation of the titanium/bone interface at this time-point indicated successful osseointegration with normal remodeled bone adjacent to the fixture. Calcitonin gene-related peptide activity was upregulated during the process of bone remodeling, and there was no significant inflammatory reaction. There was new, normal bone adjacent to and fully occupying the space between fixture threads. Innervation also appeared normal in remodeled bone, as indicated by immunohistochemical observation of small nerve fibers with the antibody Protein Gene Product 9.5 (PGP 9.5). The model will be used further to explore intramedullary osseointegration and osseoperception in connection to clinical applications.

Animals↗

Effects of phytosterols supplementation on hepatic lipid metabolism and metabolic outcomes in obese rodent models: a systematic review and meta-analysis.

This study aimed to synthesize and quantitatively assess the available evidence on the effects of phytosterol supplementation on hepatic lipid metabolism and obesity-related metabolic outcomes in obese rodent models, integrating biochemical, histological, and molecular evidence. A systematic search was conducted in electronic databases (PubMed, EMBASE, and Web of Science). Data on study design, population, intervention, outcomes, and risk of bias were extracted and analyzed. A quantitative meta-analysis was performed. Meta-analysis showed reductions in body weight, serum triglycerides, total cholesterol, LDL-C, VLDL-C, glucose, liver weight, hepatic cholesterol, hepatic triglycerides, and nonalcoholic fatty liver disease activity score. No significant changes were observed for adiposity index, HDL-C, insulin, or hepatic expression of PPAR&#x3b1;, FAS, and SREBP1c. Conversely, CPT1A expression was significantly increased following PS supplementation. Subgroup analyses indicated that the beneficial effects on lipid and hepatic outcomes were generally consistent across rodent species (mice, rats, and hamsters), obesity induction models, and routes of administration, although the magnitude of responses varied between strains, with C57BL/6 mice showing more pronounced metabolic improvements. Additional analyses suggested that treatment duration and phytosterol composition may modulate specific outcomes, whereas dose-response meta-regression identified dose-dependent associations for serum and hepatic cholesterol, and PPAR&#x3b1; expression in dietary supplementation studies. Overall, the available preclinical evidence suggests that phytosterol supplementation may improve several metabolic and hepatic outcomes in rodent models of obesity. However, the substantial heterogeneity across studies highlights the need for standardized experimental protocols and future clinical studies before these findings can be translated to human health.

Animals↗

Monitoring weight drop velocity and foam stiffness as an aid to quality control of a rodent model of impact acceleration neurotrauma.

Since the publication by Marmarou of a new rodent model of head injury, an increasing number of centres are adopting the model for use in a variety of paradigms. We report on two simple methods we have applied which allows us to monitor weight drop velocity and foam stiffness, both of which are critical factors for producing repeatable closed head injury with this model. We hope the application of these methods will assist in the standardisation of this model between centres.

Animals↗

Lung function and airway inflammation in rats following exposure to combustion products of carbon-graphite/epoxy composite material: comparison to a rodent model of acute lung injury.

Pulmonary function and inflammation in the lungs of rodents exposed by inhalation to carbon/graphite/epoxy advanced composite material (ACM) combustion products were compared to that of a rodent model of acute lung injury (ALI) produced by pneumotoxic paraquat dichloride. This investigation was undertaken to determine if short-term exposure to ACM smoke induces ALI; and to determine if smoke-related responses were similar to the pathogenic mechanisms of a model of lung vascular injury. We examined the time-course for mechanical lung function, infiltration of inflammatory cells into the lung, and the expression of three inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2) and interferon-gamma (IFN-gamma). Male Fischer-344 rats were either exposed to 26.8-29.8 g/m(3) nominal concentrations of smoke or were given i.p. injections of paraquat dichloride. Measurements were determined at 1, 2, 3, and 7 days post exposure. In the smoke-challenged rats, there were no changes in lung function indicative of ALI throughout the 7-day observation period, despite the acute lethality of the smoke atmosphere. However, the animals showed signs of pulmonary inflammation. The expression of TNF-alpha was significantly increased in the lavage fluid 1 day following exposure, which preceded the maximum leukocyte infiltration. MIP-2 levels were significantly increased in lavage fluid at days 2, 3, and 7. This followed the leukocyte infiltration. IFN-gamma was significantly increased in the lung tissue at day 7, which occurred during the resolution of the inflammatory response. The paraquat, which was also lethal to a small percentage of the animals, caused several physiologic changes characteristic of ALI, including significant decreases in lung compliance, lung volumes/capacities, distribution of ventilation, and gas exchange capacity. The expression of TNF-alpha and MIP-2 increased significantly in the lung tissue as well as in the lavage fluid. Increased MIP-2 levels also preceded the maximum neutrophil infiltration. The differences in the time-course and primary site of TNF-alpha, MIP-2, and IFN-gamma expression; and the differences in the temporal relationship between their expression and infiltration of inflammatory cells may have accounted for the differences in lung function between paraquat treated and ACM smoke exposed animals.

Animals↗