Carotid Body and Cell Therapy.

During the past decade, the carotid body (CB) has been considered an innovative therapeutic target for the treatment of certain cardiorespiratory and metabolic diseases most of which are sympathetically mediated. It has recently been revealed that CB stem cells provide new target sites for the development of promising cell-based therapies. Specifically, generation of CB progenitors in vitro which can differentiate into functionally active glomus cells may be a useful procedure to produce the cell mass required for replacement cell therapy. Due to their dopaminergic nature, adult glomus cells can be used for an intrastriatal grafting in neurodegenerative brain disorders including Parkinson's disease. The beneficial effect of throphic factors such as glial cell-derived neurotrophic factor synergistically released by the transplanted cells then enables the transplant to survive. Likewise, intracerebral administration of CB cell aggregates or dispersed cells has been tested for the treatment of an experimental model of stroke. The systematic clinical applicability of CB autotransplants following glomectomy in humans is under investigation. In such autotransplantation studies, cell aggregates from unilaterally resected CB might be used as autografts. In addition, stem cells could offer an opportunity for tissue expansion and might settle the issue of small number of glomus cells available for transplantation.

Neuroprotective and reparative effects of carotid body grafts in a chronic MPTP model of Parkinson's disease.

Intrastriatal transplantation of dopaminergic carotid body (CB) cells ameliorates parkinsonism in animal models and, with less efficacy, in Parkinson's disease patients. CB-based cell therapy was initially proposed because of its high dopamine content. However, later studies suggested that its beneficial effect might be due to a trophic action exerted on nigrostriatal neurons. Compatible with this concept are the high levels of neurotrophic factors encountered in CB cells. To test experimentally this idea, unilateral striatal transplants were performed with a sham graft in the contralateral striatum, as a robust internal control. Thereafter, the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6, -tetrahydropyridine was injected during 3 months. CB grafts protected from degeneration ipsilateral nigral dopaminergic neurons projecting to the transplant in a dose-dependent manner regarding size and glial cell line-derived neurotrophic factor expression. Grafts performed at different times after the onset of the neurotoxic treatment demonstrated with histological and behavioral methods protection and repair of the nigrostriatal pathway by CB transplants. This study provides a mechanistic explanation for the action of CB transplants on parkinsonian models. It should also help to improve cell therapy approaches to Parkinson's disease.

Cografting of carotid body cells improves the long-term survival, fiber outgrowth and functional effects of grafted dopaminergic neurons.

AIMS: A major limiting factor for cell therapy in Parkinson's disease is that the survival of grafted dopaminergic neurons is very poor, which may be improved by administration of GDNF, for which the carotid body is a good source. MATERIALS & METHODS: Rats with total unilateral dopaminergic denervation were grafted with a cell suspension of rat dopaminergic neuroblasts with or without cell aggregates from the rat carotid body. At 1, 2 and 3 months after grafting, the rats were tested in the cylinder and the rotometer and killed 4 months after grafting. RESULTS: We observed that the survival of dopaminergic neurons and graft-derived dopaminergic innervation were higher in rats that received mixed grafts. Both grafted groups showed complete recovery in the amphetamine-induced rotation test. However, rats with cografts performed significantly better in the cylinder test. CONCLUSION: Cografting of carotid body cells may constitute a useful strategy for cell therapy in Parkinson's disease.

The neurogenic niche in the carotid body and its applicability to antiparkinsonian cell therapy.

The carotid body (CB) is a neural crest-derived organ whose major function is to sense changes in arterial O(2) tension to elicit hyperventilation during hypoxia. The CB is composed of clusters of neuron-like glomus, or type I, cells that are highly dopaminergic and contain large amounts of the glial cell line-derived neurotrophic factor (GDNF). Glomus cells are enveloped by glia-like sustentacular, or type II, cells. In chronic hypoxia the CB grows with increase in glomus cell number. This adaptive response depends on a collection of neural progenitors that can be isolated and induced to form clonal neurospheres in vitro. CB neurospheres contain numerous newly differentiated glomus cells, which maintain their functional properties and the ability to synthesize dopamine and GDNF. Intrastriatal CB transplants have been assayed in animal models of Parkinson's disease (PD) to test whether they increase the striatal dopamine levels and/or exert a neuroprotective action on the nigrostriatal pathway. Two pilot safety studies performed on PD patients subjected to CB autotransplantation have suggested that a major limitation of this technique is the small size of the organ. This could, however, be overcome by the in vitro formation of new CB tissue derived from adult CB stem cells.

Trophic factors in the carotid body.

The aim of the present study is to provide a review of the expression and action of trophic factors in the carotid body. In glomic type I cells, the following factors have been identified: brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, artemin, ciliary neurotrophic factor, insulin-like growth factors-I and -II, basic fibroblast growth factor, epidermal growth factor, transforming growth factor-alpha and -beta1, interleukin-1beta and -6, tumour necrosis factor-alpha, vascular endothelial growth factor, and endothelin-1 (ET-1). Growth factor receptors in the above cells include p75LNGFR, TrkA, TrkB, RET, GDNF family receptors alpha1-3, gp130, IL-6Ralpha, EGFR, FGFR1, IL1-RI, TNF-RI, VEGFR-1 and -2, ETA and ETB receptors, and PDGFR-alpha. Differential local expression of growth factors and corresponding receptors plays a role in pre- and postnatal development of the carotid body. Their local actions contribute toward producing the morphologic and molecular changes associated with chronic hypoxia and/or hypertension, such as cellular hyperplasia, extracellular matrix expansion, changes in channel densities, and neurotransmitter patterns. Neurotrophic factor production is also considered to play a key role in the therapeutic effects of intracerebral carotid body grafts in Parkinson's disease. Future research should also focus on trophic actions on carotid body type I cells by peptide neuromodulators, which are known to be present in the carotid body and to show trophic effects on other cell populations, that is, angiotensin II, adrenomedullin, bombesin, calcitonin, calcitonin gene-related peptide, cholecystokinin, erythropoietin, galanin, opioids, pituitary adenylate cyclase-activating polypeptide, atrial natriuretic peptide, somatostatin, tachykinins, neuropeptide Y, neurotensin, and vasoactive intestinal peptide.

Striatal carotid body graft promotes differentiation of neural progenitor cells into neurons in the olfactory bulb of adult hemiparkisonian rats.

Progenitor cells generated in the subventricular zone (SVZ) migrate toward the olfactory bulb (OB), where they differentiate into neurons. Growth factors have been shown to promote neurogenesis in the SVZ/OB-system while dopaminergic lesion exerts an opposite effect. As carotid body (CB) cells express growth factors here we study the impact of intrastriatal CB graft on migration and differentiation of neural progenitor cells in the hemiparkinsonian rat SVZ/OB-system. Bromodeoxyuridine (BrdU) was given to intact, 6-hydroxydopamine (6-OHDA)-lesioned and 6-OHDA-lesioned animals transplanted with vehicle or rat CB cells. The migration of progenitor cells was assessed by the quantification of BrdU-labeled cells in the SVZ/OB-system and the neuronal differentiation by the proportion of newborn neurons in the OB. The graft survival was confirmed by CB cell morphology and their tyrosine hydroxylase expression. Some of these CB cells were stained with BrdU, thus indicating their ability for self-renewal. Grafted glomus cells also expressed brain derived neurotrophic factor (BDNF), glial derived neurotrophic factor (GDNF), epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF). The migration of neural progenitor cells was significantly decreased in 6-OHDA-lesioned respect to intact animals. We found a similar number of BrdU-labeled cells in sham-operated than in CB-grafted animals, suggesting that CB graft has no effect on progenitor cell migration. CB-grafted animals exhibited a significantly larger percentage of newborn cells (BrdU/Neuronal Nuclei-labeled cells) respect to 6-OHDA-lesioned and sham-operated animals. This study suggests that striatal CB graft might promote differentiation of SVZ progenitor cells into neurons, probably by the growth factors contained in CB cells.

Modification of the number and phenotype of striatal dopaminergic cells by carotid body graft.

In non-human primates, striatal tyrosine hydroxylase-immunoreactive (TH-ir) cells are increased in number after dopamine depletion and in response to trophic factor delivery. As carotid body cells contain the dopaminotrophic glial cell line-derived neurotrophic factor (GDNF), we evaluated the number, morphology and neurochemistry of these TH-ir cells, in the anterior and posterior striatum of five monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which received a graft of carotid body cell aggregates (CBCA) (n = 3) or sham surgery (n = 2), and six MPTP-monkeys that were sacrificed 6 months and 3 years after the last MPTP dose [MPTP I (n = 3) and MPTP II (n = 3), respectively]. Three intact monkeys served as controls. A disability rating scale was used for the assessment of parkinsonism in all lesioned animals, both before and after surgery. For the neurochemical examination, tissue sections were double-labelled with antibodies to TH, dopamine transporter, dopa decarboxylase-67, vesicular monoamine transporter 2, glutamic acid decarboxylase -67, calbindin, parvalbumin, calretinin, neuronal nitric oxide synthase and GDNF. Only animals receiving CBCA graft showed a moderate but significant recovery of parkinsonism that persisted 12 months after the graft. The grafted striatum contained the greatest TH-ir cell density (120.4 +/- 10.3 cells/100 mm2), while the control striatum displayed the lowest (15.4 +/- 6.8 cells/100 mm2), and MPTP I, MPTP II and sham-operated monkeys showed a similar intermediate value (66.1 +/- 6.2, 58.3 +/- 17.2 and 57.7 +/- 7.0 cells/100 mm2, respectively). In addition, in the post-commissural striatum, only CBCA graft induced a significant increase in the TH-ir cell density compared to control animals (47.9 +/- 15.9 and 7.9 +/- 3.2, respectively). Phenotypically, TH-ir cells were striatal dopaminergic interneurons. However, in the grafted animals, the phenotype was different from that in control, MPTP and sham-operated monkeys, with the appearance of TH/GDNF-ir cells and the emergence of two TH-ir subpopulations of different size as the two main differentiating features. Our data confirm and extend previous studies demonstrating that striatal CBCA grafts produce a long-lasting motor recovery of MPTP-monkeys along with an increase in the number and phenotype changes of the striatal TH-ir interneurons, probably by the action of the trophic factors contained in carotid body cells. The increased number of striatal TH-ir cells observed in the grafted striatum may contribute to the improvement of parkinsonism observed after the graft.

Transplantation of carotid body cells in the treatment of neurological disorders.

Laboratory and clinical studies have shown that intracerebral transplantation of carotid body (CB) cells ameliorate Parkinsonian deficits. The recent clinical study by Arjona and colleagues indicated that CB autograft transplantation is a relatively simple, safe, and viable treatment for PD patients. In particular, Espejo and colleagues demonstrated that the therapeutic efficacy of intracerebral transplantation of the CB in PD was likely obtained through secretion of neurotrophic factors rather than the local release of dopamine, which suggests it possible and reasonable to extend the use of the CB as an efficacious graft source for neural transplantation. Thus, we transplanted CB cell suspensions into the ischemic penumbra within 1h after stroke surgery. The results revealed that CB transplantation also significantly reduced stroke-induced behavioral deficits and cerebral infarction. In this review, we focus on summarizing the physiological properties of the CB related to transplantation, describing briefly possible mechanisms responsible for the effect of CB transplantation, and introducing recent studies of the CB as a donor source for neural transplantation.

Electrophysiological properties of rat nodose ganglion neurons co-transplanted with carotid bodies into the chick chorioallantoic membrane.

The electrophysiological properties of nodose ganglion neurons were evaluated immediately after removing nodose ganglia from young adult rats and 3 to 10 days after nodose ganglia implantation -either alone or co-implanted with carotid bodies- onto the chick chorioallantoic membrane. Implanted and co-implanted nodose neurons were less excitable than acutely recorded nodose neurons. Co-implanted neurons also showed reduced amplitudes for both action potentials and spike after-hyperpolarizations relative to those found in. acutely recorded nodose ganglion neurons and a smaller time constant (T) than that found in implanted neurons. In addition, no spontaneous activity was recorded from nodose ganglion neurons co-implanted with carotid bodies during 3-9 days, which suggests that functional synapses between carotid glomus cells and nodose neurons were not yet established. Results indicate the feasibility of obtaining viable nodose neurons for up to 10 days grafted onto the chick chorioallantoic membrane, where they can conserve most of their passive and active membrane properties and also are susceptible to carotid bodies trophic influences. They also suggest that nodose neurons would need more time for the development of functional synapses when grafted with carotid body glomus cells.

Electrophysiological properties of rat nodose ganglion neurons co-transplanted with carotid bodies into the chick chorioallantoic membrane

The electrophysiological properties of nodose ganglion neurons were evaluated immediately after removing nodose ganglia from young adult rats and 3 to 10 days after nodose ganglia implantation _either alone or co-implanted with carotid bodies_ onto the chick chorioallantoic membrane. Implanted and co-implanted nodose neurons were less excitable than acutely recorded nodose neurons. Co-implanted neurons also showed reduced amplitudes for both action potentials and spike after-hyperpolarizations relative to those found in acutely recorded nodose ganglion neurons and a smaller time constant (ô) than that found in implanted neurons. In addition, no spontaneous activity was recorded from nodose ganglion neurons co-implanted with carotid bodies during 3-9 days, which suggests that functional synapses between carotid glomus cells and nodose neurons were not yet established. Results indicate the feasibility of obtaining viable nodose neurons for up to 10 days grafted onto the chick chorioallantoic membrane, where they can conserve most of their passive and active membrane properties and also are susceptible to carotid bodies trophic influences. They also suggest that nodose neurons would need more time for the development of functional synapses when grafted with carotid body glomus cells.

Co-transplantation of carotid body and ventral mesencephalic cells as an alternative approach towards functional restoration in 6-hydroxydopamine-lesioned rats: implications for Parkinson's disease.

Exogenous administration of various neurotrophic factors has been shown to protect neurons in animal model of Parkinson's disease (PD). Several attempts are being made to search a tissue source simultaneously expressing many of these neurotrophic factors. Carotid body (CB) contains oxygen-sensitive glomus cells rich in dopamine (DA) and expresses glial cell line-derived neurotrophic factor, brain-derived neurotrophic factor and neurotrophin-3. We have attempted to study the functional restoration following co-transplantation of CB cells and ventral mesencephalic cells (VMC) in a 6-hydroxydopamine-lesioned rat model of PD. A significant recovery (p < 0.001) in d-amphetamine-induced circling behavior (80%) and spontaneous locomotor activity (85%) was evident in co-transplanted animals at 12 weeks post-transplantation as compared to lesioned animals. Similarly, a significant (p < 0.001) restoration was observed in DA-D(2) receptor binding (77%), striatal DA (87%) and 3,4-dihydroxyphenylacetic acid (DOPAC) (85%) levels and nigral DA (75%) and DOPAC (74%) levels. Functional recovery was accompanied by tyrosine hydroxylase (TH) expression and quantification of TH-positive cells by image analysis revealed a significant restoration in TH-immunoreactive (IR) fiber density in striatum, as well as TH-IR neurons in substantia nigra pars compacta in co-transplanted animals over VMC-transplanted animals. The result suggests that co-transplantation of CB cells along with VMC provides better and long-term functional restoration in the rat model of PD, possibly by supporting the survival of newly grafted cells as well as remaining host DA neurons.

Intracerebral transplantation of carotid body in rats with transient middle cerebral artery occlusion.

Recent laboratory and clinical studies demonstrate therapeutic efficacy of intracerebral transplantation of carotid body (CB) in Parkinson's disease, possibly through secretion of neurotrophic factors. Here, we examined the role of CB in experimental stroke. In the first experiment, we hypothesized that removal of CB would exacerbate cerebral infarction and stroke-related behavioral deficits. Eight-week-old, male Sprague-Dawley rats were randomly divided into two groups: stroke with intact CB and stroke with surgically removed CB. We used the stroke model of temporary middle cerebral artery occlusion. The ipsilateral CB was removed in animals assigned to treatment group exposed to stroke with surgically removed CB. Behavioral tests, using the elevated body swing test, were conducted at days 1-3 after surgery. Cerebral infarction was visualized by TTC staining on day 3 post-surgery. The data revealed no significant differences in behavioral deficits and infarct volumes between the two groups. In the second experiment, CB cell suspension grafts or control adult tissue grafts were intracerebally transplanted into the ischemic penumbra immediately (within 1 h) after stroke surgery. The results revealed significant reduction of behavioral deficits and infarct volumes, accompanied by increased levels of neurotrophic factors, as detected by ELISA, in transplanted ischemic striatum collected from CB-grafted stroke animals. These observations suggest that surgical resection of CB in the periphery did not alter stroke pathology; however, CB when made available in the CNS, via intracerebral transplantation, could protect against stroke possibly through the synergistic release of neurotrophic factors. The present study extends the use of CB as efficacious graft source for transplantation.

Autotransplantation of human carotid body cell aggregates for treatment of Parkinson's disease.

OBJECTIVE: In this study, we assessed the feasibility of autotransplantation of carotid body (CB) cell aggregates into the striatum for the treatment of patients with Parkinson's disease (PD). METHODS: Six patients with advanced PD underwent bilateral autotransplantation of CB cell aggregates into the striatum. They were evaluated clinically preoperatively and for 18 months after surgery according to the recommendations of the Core Assessment Program for Intracerebral Transplantation. RESULTS: No major complications or adverse events resulted from the cell implantation or surgical procedures. During the course of the study, there was no significant aggravation of dyskinesia or decline in cognitive function in any of the patients. Five of the six patients who underwent transplantation manifested a measurable degree of clinical improvement evidenced by standardized clinical rating scales for PD. A decrease in the blinded Unified Parkinson's Disease Rating Scale Part III in the "off" state, the main measure of transplant efficacy in our study, was found to be maximal (between 26 and 74%) at 6 months after surgery. At 1 year, clear reductions in the blinded Unified Parkinson's Disease Rating Scale Part III were maintained in three patients (24, 38, and 52%, respectively). Modest improvement was seen in two patients (13 and 17%), and the sole patient who showed no improvement had the most fibrosis in the CB. The age of the patient and the state of the CB tissue were adversely correlated with clinical improvement after CB autotransplantation. CONCLUSION: This pilot study indicates that CB autograft transplantation is a relatively simple, safe, and viable therapeutical approach for the treatment of patients with advanced PD. More studies are needed to optimize the procedure and to assess its general applicability for the treatment of patients with PD.

Trophic restoration of the nigrostriatal dopaminergic pathway in long-term carotid body-grafted parkinsonian rats.

We studied the mechanisms underlying long-term functional recovery of hemiparkinsonian rats grafted intrastriatally with carotid body (CB) cell aggregates. Amelioration of their motor syndrome is a result of the trophic actions of these grafts on the remaining ipsilateral substantia nigra neurons rather than of the release of dopamine from the CB grafts. The grafts maintain a stable morphological appearance and differentiated cell phenotype for the duration of the life of the host. Adult CB expresses high levels of glial cell line-derived neurotrophic factor (GDNF) and the multicomponent GDNF receptor complex. These properties may contribute to the trophic actions of the CB transplants on nigrostriatal neurons and to their extraordinary longevity. We show that CB glomus cells, although highly dopaminergic, are protected from dopamine-mediated oxidative damage because of the absence of the high-affinity dopamine transporter. Thus, intrastriatal CB grafts are uniquely suited for long-term delivery of trophic factors capable of promoting restoration of the nigrostriatal pathway.

Dynamic expression of bFGF and TGFbeta2 in glomus cell grafts of carotid body in rat model of Parkinson disease.

To investigate the changes in the expression of basic fibroblast growth factor (bFGF) and transforming growth factor beta 2 (TGFbeta2) in glomus cell grafts of carotid body in the rat model of 6-hydroxydopamine-induced Parkinson disease, immunohistochemical staining of bFGF and TGFbeta2 in the sections of striate body was done on the 2nd, 4th and 12th week after transplantation. The results showed that on the 2nd week after transplantation, bFGF and TGFbeta2 were not detectable in the glumous cell grafts. On the 4th week after graft, bFGF and TGFbeta2 immunoreactivity was increased within the grafts and at the graft-host interface but was restricted only to astrocytes. In the striatum surrounding the graft, bFGF was expressed persistently, while TGFbeta2 showed transient expression. It was suggested that the transient expression of TGFbeta2 was likely due more to the trauma imposed by the graft procedure than to an intrinsic. The deficiency in astrocytic bFGF early after graft may be responsible for the poor survival of grafted glomus cells of carotid body.

Dopaminergic cells of the carotid body: physiological significance and possible therapeutic applications in Parkinson's disease.

Parkinson's disease is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra projecting to the striatum. One therapeutic approach to this disease has been the intrastriatal transplantation of dopamine-secreting cells. We have investigated the suitability of glomus cells of the carotid body for dopamine-cell replacement in animal models of Parkinson's disease. Carotid body glomus cells are physiologic arterial oxygen sensors that release large amounts of dopamine in response to hypoxia. We have used hemi-Parkinsonian rats, induced by injection of 6-hydroxydopamine into the substantia nigra, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treated monkeys with chronic Parkinsonism. In both cases we made transplants of carotid body cell aggregates into the putamen. Functional recovery of the grafted animals was observed after the surgery and was stable for several months. Although the study was more detailed in the rat, in the two animal models the amelioration of the motor deficits was paralleled by striatal dopaminergic reinnervation and survival of grafted glomus cells. Our results suggest that intrastriatal autotransplants of carotid body tissue could be a feasible technique to treat some cases of Parkinson's disease in humans.

Experimental study on heterograft of glomus cells of carotid body for hemiparkinsonian rats.

To observe the effects of heterograft of glomus cells of carotid body on hemiparkinsonian rat models, rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the right dopaminergic neurons of substantia nigra received intrastriatal glomus cells heterograft. Apomorphine-induced rotation was monitored for 30 min at various time points after grafting. The striata were cut and examined for dopamine content by HPLC and for immunohistochemical staining of tyrosine hydroxylase positive neurons (TH+) at the end of the experiments. The results showed that apomorphine-induced rotational behavior was significantly reduced for 12 weeks and the dopamine contents were significantly elevated after grafting (P < 0.01), and TH+ cells survived better. The present study demonstrates that intrastriatal heterograft of glomus cells within carotid body in rats with 6-OHDA-elicited lesions could reduce apomorphine-induced rotational behavior and elevate the dopamine contents and numbers of TH+ cell surviving within striatum, and can serve as a new and effective alternative for Parkinson disease.

Intrastriatal grafting of glomus cells ameliorates behavioral defects of Parkinsonian rats.

Parkinson's disease is associated with severe motor dysfunctions due to a progressive loss of dopaminergic neurons in substantia nigra. Transplantation of midbrain neurons from human fetuses to the striatum of patients provides effective treatment for the disease. This type of approach, however, could not be adopted widely due to insufficient supply of fetal materials and the controversial ethical and legal issues. The carotid body is a chemoreceptive organ containing chromaffin-like glomus cells that secrete dopamine (DA) as the neurotransmitter. Here, we report the generation of a clonal dopaminergic cell line of the carotid body using the H-2K(b)-tsA58 transgenic mouse. Cells from the carotid body were immortalized at the permissive temperatures and in the presence of gamma-interferon. The glomus cells were isolated by flow cytometry, and purified to homogeneity by a limited dilution procedure. Upon switching the culture to a nonpermissive condition, the immortal cells ceased to divide, became terminally differentiated and secreted high levels of DA. In rats rendered hemi-Parkinsonian by injection of 6-hydroxydopamine (6-OHDA) into the substantial nigra, intrastriatal grafting of the glomus cells resulted in significant recovery of motor asymmetries and sensorimotor dysfunction. The effects were apparent approximately 10 days after transplantation and remained throughout the 4 months of the study. The recovery of behavioral defects was correlated with the ability of cell grafts to release DA in the brain. As none of the existing treatments for Parkinson's disease is completely satisfactory, establishment of a clonal cell line that secretes DA opens a new avenue for the effective control of this neurological disorder.

Experimental study on heterograft of glomus cells of carotid body for hemiparkinsonian rats / 华中科技大学学报（医学）（英德文版）

To observe the effects of heterograft of glomus cells of carotid body on hemiparkinsonian rat models, rats with unilateral 6-hydroxydopamine (6-OHDA)-induced lesions of the right dopaminergic neurons of substantia nigra received intrastriatal glomus cells heterograft. Apomorphine-induced rotation was monitored for 30 min at various time points after grafting. The striata were cut and examined for dopamine content by HPLC and for immunohistochemical staining of tyrosine hydroxylase positive neurons (TH+) at the end of the experiments. The results showed that apomorphine-induced rotational behavior was significantly reduced for 12 weeks and the dopamine contents were significantly elevated after grafting (P < 0.01), and TH+ cells survived better. The present study demonstrates that intrastriatal heterograft of glomus cells within carotid body in rats with 6-OHDA-elicited lesions could reduce apomorphine-induced rotational behavior and elevate the dopamine contents and numbers of TH+ cell surviving within striatum, and can serve as a new and effective alternative for Parkinson disease.