Intractable migraine headaches during pregnancy under chiropractic care.

The absence of hormone fluctuations and/or the analgesic effects of increased beta-endorphins are thought to confer improvements in headache symptoms during pregnancy. However, for a number of pregnant patients, they continue to suffer or have worsening headache symptoms. The use of pharmacotherapy for palliative care is a concern for both the mother and the developing fetus and alternative/complementary care options are sought. We present a 24-year-old gravid female with chronic migraine headaches since age 12years. Previous unsuccessful care included osteopathy, physical therapy, massage and medication. Non-steroidal anti-inflammatory medication with codeine provided minor and temporary relief. Chiropractic care involving spinal manipulative therapy (SMT) and adjunctive therapies resulted in symptom improvement and independence from medication. This document provides supporting evidence on the safety and possible effectiveness of chiropractic care for patients with headaches during pregnancy.

Neurochemical characterization of dopaminergic neurons in human striatum.

We examined the neurochemical phenotype of striatal neurons expressing tyrosine hydroxylase (TH) mRNA to determine if they form a distinct class of neurons within the human striatum. Double in situ hybridization (ISH) and immunohistochemical (IHC) procedures were used to know if TH mRNA-positive striatal neurons express molecular markers of mature neurons (MAP2 and NeuN), dopaminergic neurons (DAT and Nurr1) or immature neurons (TuJ1). All TH mRNA-labeled neurons were found to express NeuN, DAT and Nurr1, whereas about 80% of them exhibited MAP2, confirming their neuronal and dopaminergic nature. Only about 30% of TH mRNA-labeled neurons expressed TuJ1, suggesting that this ectopic dopaminergic neuronal population is principally composed of mature neurons. The same double ISH/IHC approach was then used to know if these dopamine neurons display markers of well-established classes of striatal projection neurons (GAD65 and calbindin) or local circuit neurons (GAD65, calretinin, somatostatin and parvalbumin). Virtually all TH-labeled neurons expressed GAD65 mRNA, about 30% of them exhibited calretinin, but none stained for the other striatal neuron markers. These results suggest that the majority of TH-positive neurons intrinsic to the human striatum belong to a distinct subpopulation of striatal interneurons characterized by their ability to produce dopamine and GABA.

Morphology and distribution of dopaminergic neurons intrinsic to the human striatum.

The putative dopaminergic (DA) neurons intrinsic to the human striatum were studied by applying immunofluorescence and quantitative methods to postmortem tissue from seven normal individuals. Stringent morphological and chemical criteria were used to identify striatal DA neurons, including immunostaining for tyrosine hydroxylase, DA transporter and neuronal nuclear protein. The DA neurons were scattered throughout the striatum, but abounded particularly in its ventral portion. Frequency distribution of surface areas of DA cell bodies reveals that the most frequent DA neurons (x =58.0%, S.D.=12.8%) had a medium-sized (approximately 200+/-15 microm2) perikaryon with 3-5 varicose dendrites, whereas others (x =35.5%, S.D.=14.0%) had a smaller (approximately 140+/-15 microm2) perikaryon with 3-4 varicose dendrites. There was a small number (x =6.5%, S.D.=8.5%) of larger DA neurons (209-584 microm2) with spiny dendrites and a few TH-immunoreactive cells displaying mixed neuron-glia morphology. Despite significant inter-individual variations in neuron density, the human striatum (mean volume of 8.76 cm3) harbored a mean of 331.9 DA neurons (S.D.=199.2). A prolific zone, containing about 3000 cells, occurred in the ventral striatum in two brains. The addition of these cells would increase by about 10 times the total number of striatal DA neurons, which should not be confounded with segments of nigrostriatal DA fibers that displayed large (8-12 microm) varicosities and looked like small bipolar neurons. The function of striatal DA neurons is unknown but the fact that their number increases markedly following lesion of nigral DA input or administration of various growth factors, opens up new therapeutic avenues for treatment of Parkinson's disease.

Tyrosine hydroxylase-positive neurons intrinsic to the human striatum express the transcription factor Nurr1.

The putative dopaminergic (DA) neurons intrinsic to human striatum were studied to determine their similarity with DA neurons of the substantia nigra pars compacta (SNpc). The comparison was based on morphological features and on the presence or absence of Nurr1, an orphan receptor of the nuclear receptor family that is essential for the expression of DA phenotype by developing SNpc neurons. Immunohistochemistry for the neuronal nuclear protein (NeuN; a neuronal marker) and in situ hybridization for tyrosine hydroxylase (TH) and/or Nurr1 were applied to post-mortem tissue obtained from seven normal individuals. On one hand, the TH-positive multipolar neurons in the human striatum, which were subdivided into three groups according to their size and pattern of dendritic arborization, were found to be morphologically similar to TH-positive neurons of the SNpc. The distribution frequency of striatal TH-positive neurons, according to their diameter, closely matches the frequency observed for multipolar TH-positive cells in the SNpc. On the other hand, the proportion of neurons expressing Nurr1 and TH mRNA transcripts on single striatal section was similar to the proportion of TH-immunoreactive neurons observed on adjacent sections. More importantly, in each striatum analysed, virtually all cells that stained for TH also expressed NeuN and Nurr1. This study provides novel data that confirm the existence of DA neurons intrinsic to the human striatum. It also provides the first evidence for the existence of striking morphological and chemical similarities between the DA neurons present at striatal level and those that populate the SNpc.

Novel aspects of the chemical anatomy of the striatum and its efferents projections.

This paper summarizes the results of some of our previous neuroanatomical and immunohistochemical studies on the organization of the striatum and its efferent projections in rodents, monkeys and humans. It also reports recent functional calcium-imaging data obtained in rat brain slices, as well as developmental results gathered with bromodeoxyuridine (BrdU) in monkeys. On one hand, single-axon tracing studies in rats and monkeys have revealed that the majority of striatofugal axon arborizes within most striatal target structures. In humans, SP-positive fibers were found to arborize in the two segments of the globus pallidus, where they were closely apposed to pallidal neurons that expressed the neurokinin-1 receptor (NK-1r). In agreement with such findings, calcium-imaging studies in rats have revealed that pallidal and nigral neurons are both responsive to SP. These findings suggest that the striatofugal projection system is much more widely distributed than previously thought and exerted a multifaceted effect upon its target sites. On the other hand, immunostaining studies in humans have shown the presence of several types of putative dopaminergic neurons intrinsic to the striatum. Furthermore, BrdU labeling experiments in monkeys have demonstrated that new neurons are generated throughout adult life in the striatum of normal monkeys and that their number can be markedly increased by the administration of neuronal growth factors. These findings open new therapeutic avenues for the treatment of neurodegenerative disorders that specifically affect the striatum.

Proliferating cells can differentiate into neurons in the striatum of normal adult monkey.

In this study we used bromodeoxyuridine (BrdU), a thymidine analogue that is incorporated into the DNA of mitotic cells, to study the cytogenesis status of the striatum in normal, adult, squirrel monkeys (Saimiri sciureus). Three weeks following BrdU injection, numerous BrdU-labeled (+) cells were encountered within both the dorsal and the ventral striatum, including the nucleus accumbens. Their number ranged from 5 to 50 per 40 microm-thick section. These BrdU+ cells were more abundant medially than laterally and displayed a rostrocaudal-decreasing gradient in the caudate nucleus and putamen. Double-immunofluorescence confocal studies have revealed that about 5-10% of the BrdU+ striatal cells expressed the neuronal nuclear antigen (NeuN), a marker for mature neurons. These findings suggest that new neurons are produced throughout adult life in the striatum of normal, adult primates. This result raises the possibility of experimentally enhancing the recruitment of these newborn neurons as a means to alleviate the symptoms of neurodegenerative diseases that affect the striatum.