Effects of severity of host striatal damage on the morphological development of intrastriatal transplants in a rodent model of Huntington's disease: implications for timing of surgical intervention

1998 ◽  
Vol 89 (2) ◽  
pp. 267-274 ◽  
Author(s):  
Colin Watts ◽  
Stephen B. Dunnett
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Surgical Intervention ◽  
Rodent Model ◽  
Morphological Development ◽  
Sprague Dawley ◽  
Content Type ◽  
Striatal Grafts ◽  
The Right ◽  
Fine Print

Object. The goal of this study was to investigate the effect of the severity of host neural damage on the morphological development of intrastriatal transplants in a rodent model of Huntington's disease. Methods. Sprague—Dawley rats were subjected to unilateral striatal lesioning induced by administration of quinolinic acid (20 nM, 40 nM, or 90 nM). Seven days postlesioning, intrastriatal cell suspension grafts were placed in the right striatum in some of these animals. Grafts were also placed in the right striatum of additional animals that had not been subjected to lesioning. The rats were killed and processed for morphological analysis 8 weeks after grafting. The results indicate that striatal grafts survive and grow much better when implanted into a lesioned striatum rather than into an intact striatum, as measured both by the volume and the numbers of medium-sized spiny neurons within the graft. Only a small or modest lesion is necessary to produce this effect. By some measures (such as graft volume) grafts survive less well when the lesion is more extensive. The presence of a graft reduced the extent of striatal atrophy induced by the lesions, but this effect was not caused by differences in the numbers of surviving neurons per se. Conclusions. These results have significant implications for the timing of surgical intervention and patient selection with respect to current and future clinical trials of striatal transplantation in the treatment of Huntington's disease.

Bilateral Fetal Striatal Grafts in the 3-Nitropropionic Acid-Induced Hypoactive Model of Huntington's Disease

1998 ◽  
Vol 7 (2) ◽  
pp. 131-135 ◽  
Author(s):  
Cesario V. Borlongan ◽  
Theodore K. Koutouzis ◽  
Stephen G. Poulos ◽  
Samuel Saporta ◽  
Paul R. Sanberg
Keyword(s):  
Locomotor Activity ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Fetal Tissue ◽  
Sprague Dawley ◽  
Locomotor Apparatus ◽  
Nitropropionic Acid ◽  
Fetal Tissue Transplantation ◽  
Striatal Grafts ◽  
3 Nitropropionic Acid

We investigated the 3-nitropropionic acid (3-NP)–induced hypoactive model of Huntington's disease (HD) to demonstrate whether fetal tissue transplantation can ameliorate behavioral deficits associated with a more advanced stage of HD. Twelve-week-old Sprague–Dawley rats were introduced to the 3-NP dosing regimen (10 mg/kg, i.p., once every 4 days for 28 consecutive days), and were then tested for general spontaneous locomotor activity in the Digiscan locomotor apparatus. All rats displayed significant hypoactivity compared to their pre-3-NP injection locomotor activity. Randomly selected rats then received bilateral intrastriatal solid grafts of fetal striatal (lateral ganglionic eminence, LGE) tissues from embryonic day 14 rat fetuses. Approximately 1/3 of each LGE in hibernation medium was infused into each lesioned host striatum. In control rats, medium alone was infused intrastriatally. A 3-mo posttransplant maturation period was allowed prior to locomotor activity testing. Animals receiving fetal LGE grafts exhibited a significant increase in locomotor activity compared to their post-3-NP injection activity or to the controls’ posttransplant activity. Surviving striatal grafts were noted in functionally recovered animals. This observation supports the use of fetal striatal transplants to correct the akinetic stage of HD. To the best of our knowledge, this is the first study that has investigated the effects of fetal striatal transplantation in a hypoactive model of HD.

Malignant astrocytoma following radiotherapy of a craniopharyngioma

1978 ◽  
Vol 48 (4) ◽  
pp. 622-627 ◽  
Author(s):  
Richard L. Sogg ◽  
Sarah S. Donaldson ◽  
Craig H. Yorke
Keyword(s):  
Experimental Evidence ◽  
Temporal Lobe ◽  
Malignant Astrocytoma ◽  
Content Type ◽  
Suprasellar Region ◽  
The Right ◽  
Fine Print

✓ A 9-year-old schoolgirl received 6007 rads to the suprasellar region for craniopharyngioma. Five years later, a malignant astrocytoma developed in the right temporal lobe. We cite clinical and experimental evidence to support our suspicion that the glioma may have been induced by radiation.

A new rat model of chronic cerebral hypoperfusion associated with arteriovenous malformations

2002 ◽  
Vol 97 (5) ◽  
pp. 1198-1202 ◽  
Author(s):  
Jian Hai ◽  
Meixiu Ding ◽  
Zhilin Guo ◽  
Bingyu Wang
Keyword(s):  
Electron Microscopy ◽  
Animal Model ◽  
Arteriovenous Malformations ◽  
Perfusion Pressure ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Model Group ◽  
Content Type ◽  
The Right ◽  
Fine Print

Object. A new experimental model of chronic cerebral hypoperfusion was developed to study the effects of systemic arterial shunting and obstruction of the primary vessel that drains intracranial venous blood on cerebral perfusion pressure (CPP), as well as cerebral pathological changes during restoration of normal perfusion pressure. Methods. Twenty-four Sprague—Dawley rats were randomly assigned to either a sham-operated group, an arteriovenous fistula (AVF) group, or a model group (eight rats each). The animal model was readied by creating a fistula through an end-to-side anastomosis between the right distal external jugular vein (EJV) and the ispilateral common carotid artery (CCA), followed by ligation of the left vein draining the transverse sinus and bilateral external carotid arteries. Systemic mean arterial pressure (MAP), draining vein pressure (DVP), and CPP were monitored and compared among the three groups preoperatively, immediately postoperatively, and again 90 days later. Following occlusion of the fistula after a 90-day interval, blood—brain barrier (BBB) disruption and water content in the right cortical tissues of the middle cerebral artery territory were confirmed and also quantified with transmission electron microscopy. Formation of a fistula resulted in significant decreases in MAP and CPP, and a significant increase in DVP in the AVF and model groups. Ninety days later, there were still significant increases in DVP and decreases in CPP in the model group compared with the other groups (p < 0.05). Damage to the BBB and brain edema were noted in animals in the model group during restoration of normal perfusion pressure by occlusion of the fistula. Electron microscopy studies revealed cerebral vasogenic edema and/or hemorrhage in various amounts, which correlated with absent astrocytic foot processes surrounding some cerebral capillaries. Conclusions. The results demonstrated that an end-to-side anastomosis between the distal EJV and CCA can induce a decrease in CPP, whereas a further chronic state of cerebral hypoperfusion may be caused by venous outflow restriction, which is associated with perfusion pressure breakthrough. This animal model conforms to the basic hemodynamic characteristics of human cerebral arteriovenous malformations.

Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist clinically effective for the treatment of cerebral vasospasm. Part I: Inhibitory effect on endothelinA receptor—mediated contraction

2005 ◽  
Vol 102 (6) ◽  
pp. 1101-1107 ◽  
Author(s):  
Hartmut Vatter ◽  
Michael Zimmermann ◽  
Veronika Tesanovic ◽  
Andreas Raabe ◽  
Lothar Schilling ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Cerebral Vasospasm ◽  
Isometric Force ◽  
Inhibitory Effect ◽  
Affinity Constant ◽  
Dependent Manner ◽  
Content Type ◽  
The Right ◽  
Fine Print

Object. The central role of endothelin (ET)—1 in the development of cerebral vasospasm after subarachnoid hemorrhage is indicated by the successful treatment of this vasospasm in several animal models by using selective ETA receptor antagonists. Clazosentan is a selective ETA receptor antagonist that provides for the first time clinical proof that ET-1 is involved in the pathogenesis of cerebral vasospasm. The aim of the present investigation was, therefore, to define the pharmacological properties of clazosentan that affect ETA receptor—mediated contraction in the cerebrovasculature. Methods. Isometric force measurements were performed in rat basilar artery (BA) ring segments with (E+) and without (E−) endothelial function. Concentration effect curves (CECs) were constructed by cumulative application of ET-1 or big ET-1 in the absence or presence of clazosentan (10−9, 10−8, and 10−7 M). The inhibitory potency of clazosentan was determined by the value of the affinity constant (pA2). The CECs for contraction induced by ET-1 and big ET-1 were shifted to the right in the presence of clazosentan in a parallel dose-dependent manner, which indicates competitive antagonism. The pA2 values for ET-1 were 7.8 (E+) and 8.6 (E−) and the corresponding values for big ET-1 were 8.6 (E+) and 8.3 (E−). Conclusions. The present data characterize clazosentan as a potent competitive antagonist of ETA receptor—mediated constriction of the cerebrovasculature by ET-1 and its precursor big ET-1. These functional data may also be used to define an in vitro profile of an ET receptor antagonist with a high probability of clinical efficacy.

Coerced training of the nondominant hand resulting in cortical reorganization: a high-field functional magnetic resonance imaging study

2004 ◽  
Vol 101 (2) ◽  
pp. 310-313 ◽  
Author(s):  
Tsutomu Nakada ◽  
Yukihiko Fujii ◽  
Ingrid L. Kwee
Keyword(s):  
Magnetic Resonance Imaging ◽  
High Field ◽  
Cortical Reorganization ◽  
Functional Magnetic Resonance ◽  
Resonance Imaging ◽  
Content Type ◽  
Hand Motion ◽  
Left Handed ◽  
The Right ◽  
Fine Print

Object. The authors investigated brain strategies associated with hand use in an attempt to clarify genetic and nongenetic factors influencing handedness by using high-field functional magnetic resonance imaging. Methods. Three groups of patients were studied. The first two groups comprised individuals in whom handedness developed spontaneously (right-handed and left-handed groups). The third group comprised individuals who were coercively trained to use the right hand and developed mixed handedness, referred to here as trained ambidexterity. All trained ambidextrous volunteers were certain that they were innately left-handed, but due to social pressure had modified their preferred hand use for certain tasks common to the right hand. Although right-handed and left-handed volunteers displayed virtually identical cortical activation, involving homologous cortex primarily located contralateral to the hand motion, trained ambidextrous volunteers exhibited a clearly unique activation pattern. During right-handed motion, motor areas in both hemispheres were activated in these volunteers. During left-handed motion, the right supplemental motor area and the right intermediate zone of the anterior cerebellar lobe were activated significantly more frequently than observed in naturally right-handed or left-handed volunteers. Conclusions. The results provide strong evidence that cortical organization of spontaneously developed right- and left-handedness involves homologous cortex primarily located contralateral to the hand motion, and this organization is likely to be prenatally determined. By contrast, coerced training of the nondominant hand during the early stages of an individual's development results in mixed handedness (trained ambidexterity), indicating cortical reorganization.

Traumatic lumbar nerve root meningocele

1973 ◽  
Vol 39 (4) ◽  
pp. 528-532 ◽  
Author(s):  
James E. McLennan ◽  
William T. McLaughlin ◽  
Stanley A. Skillicorn
Keyword(s):  
Functional Recovery ◽  
Nerve Root ◽  
Surgical Intervention ◽  
Nerve Roots ◽  
Content Type ◽  
Lumbar Nerve Root ◽  
Fine Print

✓ A patient is described who developed an acute, occult, lumbosacral nerve root meningocele following a partial traumatic avulsion of the L-4 and L-5 nerve roots accompanied by fracture of the pelvis and fibula. Almost total functional recovery ensued. The differences between acute and chronic nerve root meningoceles are discussed, as well as the possibility of surgical intervention.

The right hemisphere: neuropsychological functions

1986 ◽  
Vol 64 (5) ◽  
pp. 693-704 ◽  
Author(s):  
Kenneth M. Heilman ◽  
Dawn Bowers ◽  
Edward Valenstein ◽  
Robert T. Watson
Keyword(s):  
Emotional Disorders ◽  
Right Hemisphere ◽  
Content Type ◽  
Reading And Writing ◽  
The Past ◽  
Right Hemisphere Damage ◽  
Right Hemisphere Dysfunction ◽  
Neuropsychological Functions ◽  
The Right ◽  
Fine Print

✓ In the past two to three decades, clinicians and neuroscientists have been studying the functions of the right hemisphere. Neither hemisphere seems to be dominant in the absolute sense. Each appears to be specialized and is dominant for different functions. However, most functions require the cooperation of both hemispheres. When one is damaged, the other can often compensate for the damaged one. Lesions of the left hemisphere are associated with language (speech, reading, and writing) and praxic disorders, and lesions of the right hemisphere can result in visuospatial, attentional, and emotional disorders. The authors review some of the major behavioral disorders associated with right hemisphere dysfunction and concentrate on three major types of disorders — visuospatial, attentional, and emotional. Although not all the behavioral defects associated with right hemisphere damage can be subgrouped under these three types, they are the ones most often associated with right hemisphere lesions.

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