Hans Lindå
Karolinska Institutet
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Hans Lindå.
The New England Journal of Medicine | 2009
Hans Lindå; Anders von Heijne; Eugene O. Major; Caroline F. Ryschkewitsch; Johan Berg; Tomas Olsson; Claes Martin
We describe progressive multifocal leukoencephalopathy (PML) caused by infection with human polyomavirus JC virus in a patient with multiple sclerosis who was treated with natalizumab. The first PML symptoms appeared after 14 monthly infusions of the drug. Magnetic resonance imaging (MRI) showed a presumed multiple sclerosis lesion, and JC virus DNA was not detected on polymerase-chain-reaction (PCR) assay of cerebrospinal fluid. The patients symptoms worsened, and the diagnosis of PML was established with a more sensitive quantitative PCR assay after 16 infusions of natalizumab. Plasma exchange was used to accelerate clearance of natalizumab. Approximately 3 weeks after plasma exchange, an immune-reconstitution inflammatory syndrome appeared. JC virus DNA was no longer detectable on quantitative PCR assay, and the patients symptoms improved.
Neuroscience | 1989
Staffan Cullheim; Thomas Carlstedt; Hans Lindå; M. Risling; Brun Ulfhake
By use of intracellular recording and staining with horseradish peroxidase it was found that alpha and probably also gamma motoneurons were able to reinnervate ventral root implants after an avulsion of ventral roots at the spinal cord surface in the cat. The reinnervation of the implant was achieved after an initial growth of new axons in central nervous system tissue. Reinnervating neurons could be excited or inhibited by segmental reflex activity and their axons could conduct nerve impulses. The character of muscle twitch responses elicited by electrical stimulation of implanted roots strongly indicated that denervated muscles were reinnervated by new motor axons via the implant.
Brain Research | 1985
Hans Lindå; M. Risling; Staffan Cullheim
The intramedullary portions of motor axons in the spinal cord of adult cats were divided by longitudinal incisions in the ventral funiculus. After 7-11 weeks ventral horn neurons were injected intracellularly with horseradish peroxidase. Regenerating processes of the injected cells were studied with light- and electron-microscopical techniques. The results show that in some cases more than one axon-like myelinated regenerating process was found in a single neuron. Moreover, in such cases at least one of the processes seemed to be of dendritic origin.
The Journal of Comparative Neurology | 1996
Göran Örnung; Oleg Shupliakov; Hans Lindå; Ole Petter Ottersen; Jon Storm-Mathisen; Brun Ulfhake; Staffan Cullheim
The distribution of glycine‐ and gamma‐aminobutyric acid (GABA)‐like immunoreactivity (LI) in nerve terminals on the cell soma of motoneurons in the aldehyde‐fixed cat L7 spinal cord was examined using postembedding immunogold histochemistry in serial ultrathin sections.
Experimental Brain Research | 1992
Hans Lindå; Fredrik Piehl; Å. Dagerlind; Valerie M. K. Verge; Ulf Arvidsson; Staffan Cullheim; M. Risling; Brun Ulfhake; T. Hökfelt
SummaryIn situ hybridization histochemistry was used to detect cell bodies expressing mRNA encoding for the phosphoprotein GAP-43 in the lumbosacral spinal cord of the adult rat, cat and monkey under normal conditions and, in the cat and rat, also after different types of lesions. In the normal spinal cord, a large number of neurons throughout the spinal cord gray matter were found to express GAP-43 mRNA. All neurons, both large and small, in the motor nucleus (Rexeds lamina IX) appeared labeled, indicating that both alpha and gamma motoneurons express GAP-43 mRNA under normal conditions. After axotomy by an incision in the ventral funiculus or a transection of ventral roots or peripheral nerves, GAP-43 mRNA was clearly upregulated in axotomized motoneurons, including both alpha and gamma motoneurons. An increase in GAP-43 mRNA expression was already detectable 24 h postoperatively in lumbar motoneurons both after a transection of the sciatic nerve at knee level and after a transection of ventral roots. At this time, a stronger response was seen in the motoneurons which had been subjected to the distal sciatic nerve transection than was apparent for the more proximal ventral root lesion. An upregulation of GAP-43 mRNA could also be found in intact motoneurons located on the side contralateral to the lesion, but only after a peripheral nerve transection, indicating that the concomitant influence of dorsal root afferents may play a role in GAP-43 mRNA regulation. However, a dorsal root transection alone did not seem to have any detectable influence on the expression of GAP-43 mRNA in spinal motoneurons, while the neurons located in the superficial laminae of the dorsal horn responded with an upregulation of GAP-43 mRNA. The presence of high levels of GAP-43 in neurons has been correlated with periods of axonal growth during both development and regeneration. The role for GAP-43 in neurons under normal conditions is not clear, but it may be linked with events underlying remodelling of synaptic relationships or transmitter release. Our findings provide an anatomical substrate to support such a hypothesis in the normal spinal cord, and indicate a potential role for GAP-43 in axon regeneration of the motoneurons, since GAP-43 mRNA levels was strongly upregulated following both peripheral axotomy and axotomy within the spinal cord. The upregulation of GAP-43 mRNA found in contralateral, presumably uninjured motoneurons after peripheral nerve transection, as well as in dorsal horn neurons after a dorsal root transection, indicates that GAP-43 levels are altered not only as a direct consequence of a lesion, but also after changes in the synaptic input to the neurons.
Experimental Neurology | 1998
Hans Lindå; Henrik Hammarberg; Staffan Cullheim; Agneta Levinovitz; Mohsen Khademi; Tomas Olsson
The low expression of MHC antigens is believed to be one factor of importance contributing to the immune-privileged status of CNS neurons. We here describe that motoneurons, in contrast to other nerve cells in the lumbar spinal cord of the adult rat, express both MHC class I and beta2-microglobulin mRNA. The motoneurons also display in situ hybridization signal for IFN-gamma receptor mRNA. After a peripheral axotomy, the motoneurons show a clear upregulation of beta2-microglobulin mRNA. IFN-gamma treatment of cultured rat embryonic spinal motoneurons causes a similar upregulation of especially beta2-microglobulin. Based on these facts, we propose that spinal motoneurons can be influenced by IFN-gamma and recognized by cytotoxic CD8+ T-cells. These findings could be of relevance in the search for pathogenetic mechanisms in motoneuron-specific diseases, such as ALS.
Journal of Neuroimmunology | 1999
Hans Lindå; Henrik Hammarberg; Fredrik Piehl; Mohsen Khademi; Tomas Olsson
We demonstrate here that motoneurons and nigral dopaminergic neurons in the brainstem of the adult rat, with the exception of motoneurons innervating ocular muscles, display high levels of both MHC class I heavy chain and beta2-microglobulin mRNAs. These neurons also display interferon-gamma receptor mRNA. We find it striking that these particular neurons are those which are vulnerable to neurodegeneration in diseases such as Parkinsons disease (PD) and amyotrophic lateral sclerosis (ALS).
Brain Research Bulletin | 1993
M. Risling; Kaj Fried; Hans Lindå; Thomas Carlstedt; Staffan Cullheim
In previous studies we have demonstrated that spinal motoneurons in the adult cat can regenerate CNS-type axons through CNS scar tissue into denervated ventral roots. This scar tissue, which appears to support and sustain the growth of injured CNS axons, has been shown to have a persistent defect in the blood-brain barrier (BBB). In the present study, the binding of antibodies to nerve growth factor receptor (NGFr), laminin, collagen, and a microtubule associated protein (MAP5) was assessed with indirect immunohistochemical methods 4 days-20 weeks after a lesion in the ventral funiculus of the spinal cord. An increase in content of collagen-, laminin-, and NGFr-like immunoreactivity was observed in the scar tissue during the first 3 weeks. Although type I collagen dominated in superficial areas of the scar, type IV collagen and laminin-like immunoreactivity was observed in expanded perivascular spaces all over the lesion zone. Type IV collagen- and laminin-immunoreactive structures sometimes appeared to form strands which interconnected the ventral horn and the ventral root. Regenerating axons, as revealed by staining with MAP5 or NGFr antibodies, were observed in close association to these paths. It has been suggested that a breakdown of the BBB may play a vital role in certain types of CNS regeneration by increasing the access of blood-borne trophic factors to the lesion area. The demonstration of extracellular matrix proteins like laminin provides further evidence for the notion that the observed regenerative growth takes place in an environment that is markedly different from the normal CNS.
Brain Research | 1989
M. Risling; Hans Lindå; Staffan Cullheim; P. Franson
Previous studies have shown that, in adult cats, spinal motoneurons are able to regenerate their axons after lesions in the ventral funiculus of the spinal cord. These axons regrow through a scar tissue composed of glial processes and connective tissue elements before they enter the denervated ventral root. In the present study the integrity of the blood-brain barrier (BBB) in the lesion area was assessed by i.v. injections of horseradish peroxidase (HRP), 3 weeks to 7 months postoperatively. The lesion area in the lumbosacral spinal cord was compared with the intact cervical spinal cord and the area postrema in the light and electron microscope. The results show that the BBB fails after a ventral funiculus lesion. The BBB was not restored during the examined period. The leakage of HRP appears to be the result of a transendothelial vesicular transport. In addition, it was observed that the blood vessels in the lesion area were surrounded by wide and irregular perivascular spaces with broken outer basal laminae. Other studies on traumatic defects in the BBB have indicated that the barrier is reorganized within 4 weeks after the lesion. The possibility that a prolonged defect in the BBB after a ventral spinal cord lesion might be linked with the survival of axonal sprouts is discussed.
Journal of Neurocytology | 1992
M. Risling; Kaj Fried; Hans Lindå; Staffan Cullheim; M. Meier
SummarySpinal motoneurons have a capability to regenerate CNS-type axons after intramedullary lesions in the adult cat. Regrowing axons have been traced through CNS-type scar tissue in the ventral funiculus of the spinal cord and into adjacent ventral root fascicles. This scar tissue, which appears to support and sustain regenerating axons, has been shown to have a persistent defect in the blood-brain barrier. It has been suggested that the blood-brain barrier may play a vital role in CMS regeneration by regulating the access of blood-borne trophic factors to the lesion area. In the present study, the binding of antibodies to the human nerve growth factor receptor in the cat spinal cord was examined with immunohistochemical methods 2 days to 8 weeks after a ventral funiculus lesion. The results show that, while no neurons in the ventral horn of the control material contained nerve growth factor receptor-like immunoreactivity as revealed by fluorescence microscopy, affected motoneurons expressed nerve growth factor receptor after ventral funiculus lesion. Nerve growth factor receptor-like immunoreactivity associated to both capillaries and interstitium was present in the scar tissue. Electron microscopic examination of sections labelled with the immunogold-silver method showed that perivascular nerve growth factor receptor-like immunoreactivity was located exclusively to non-pericytic perivascular cells. These cells were abundant in the expanded capillary perivascular spaces adjacent to the traumatic lesion. Similar cells, with or without relation to blood vessels, were observed in the scar tissue and in the pia mater. In a separate set of specimens it was observed that a ventral funiculus lesion combined with ventral root avulsion, which removes denervated PNS tissue, resulted in an expression of nerve growth factor receptor-like immunoreactivity which was similar to the one observed after ventral funiculus lesion only. The results of the present study show that affected motoneurons and cells in the scar tissue express nerve growth factor receptor after ventral funiculus lesion which implies that neurotrophic factors related to nerve growth factor may be of importance for the regenerative response.