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Growth hormone (GH) and brain trauma

Growth hormone (GH) is a pleiotropic hormone with known neurotrophic effects. We aimed to study whether GH administration might be useful together with rehabilitation in the recovery of TBI patients. 13 TBI patients (8 M, 5 F; age: 6-53 years old) were studied. Time after TBI: 2.5 months to 11 years; 5 patients showed acquired GH-deficiency (GHD). Disabilities observed: cognitive disorders; motor plegias; neurogenic dysphagia (n=5), vegetative coma (n=2) and amaurosis (n=1). All but one TBI patient followed intense rehabilitation for years. Treatment consisted of GH administration (maximal dose 1 mg/day, 5 days/week, resting 15-days every 2-months, until a maximum of 8 months) and clinical rehabilitation according to the individual needs (3-4 h/day, 5 days/week, during 6-12 months). Informed consent was obtained before commencing GH administration. GH significantly increased plasma IGF-1 values (ng.mL(-1)) in both GHD and no GHD patients, being then similar between both groups (GHD: 275.6±35.6 [p<0.01 vs. baseline], no GHD: 270.2±64 [p<0.05 vs. baseline]). In all the cases clear significant improvements were observed during and at the end of the combined treatment. Cognitive improvements appeared earlier and were more important than motor improvements. Swallowing improved significantly in all TBI patients with neurogenic dysphagia (2 of them in a vegetative state). Visual performance was ameliorated in the patient with amaurosis. No undesirable side-effects were observed. Our data indicate that GH can be combined with rehabilitation for improving disabilities in TBI patients, regardless of whether or not they are GHD.

Growth hormone (GH) treatment may cooperate with locally-produced GH in increasing the proliferative response of hippocampal progenitors to kainate-induced injury

Primary objective: This study was designed to investigate the effect of growth hormone treatment on the proliferation of endogenous neural progenitor cells in the dentate gyrus (DG) of the brain stimulated by kainic acid (KA)-induced neurotoxicity. Research design: Neurotoxicity was induced by intraperitoneal injection of KA. GH treatment lasted 4 days, starting either immediately or after 10 days of administration of the neurotoxic insult. Methods and procedure: Proliferating cells were immunodetected after labelling by in vivo administration of 5-bromodeoxyuridine (BrdU). GH expression was detected by in situ hybridization and immunofluorescence. Main outcomes and results: KA administration stimulated the proliferation of hippocampal precursors and this effect was significantly enhanced by GH treatment. Hippocampal GH expression was also up-regulated in response to KA administration. Conclusions: The findings support the possibility that the proliferative response observed in the hippocampus of rats treated with KA and GH is a consequence of cooperation between the exogenous and the locally-produced hormone and their synergism with other mitogenic factors generated in response to the neurotoxic damage. Therefore, GH treatment could be used to cooperate with other physiological or pathological stimuli in order to promote cell proliferation.

Role of growth hormone (GH) in the treatment on neural diseases: from neuroprotection to neural repair.

Growth hormone (GH) is a pleiotropic hormone that exerts important functions in the control of brain development as well as in the regulation neuronal differentiation and function, together with several behavioral and psychological effects that have been linked to its modulatory actions on brain neurotransmitters. In addition, the possibility that GH may play a role on brain repair after injury has been also envisaged, and a number of reports have shown that GH administration following injury confers neuroprotection and accelerates the recovery of some neural functions. In this review we have analyzed the state of the art of GH administration in several neural diseases. Though more studies are still necessary in order to completely understand the importance of GH in these processes, the promising results obtained so far, together with the absence of untoward effects during GH therapy, encourages the development of clinical assays in order to further support the use GH treatment in neural diseases in which neuroprotection and/or neuroregeneration are involved.

Multiple Effects of Growth Hormone in the Body: Is it Really the Hormone for Growth?:

In this review, we analyze the effects of growth hormone on a number of tissues and organs and its putative role in the longitudinal growth of an organism. We conclude that the hormone plays a very important role in maintaining the homogeneity of tissues and organs during the normal development of the human body or after an injury. Its effects on growth do not seem to take place during the fetal period or during the early infancy and are mediated by insulin-like growth factor I (IGF-I) during childhood and puberty. In turn, IGF-I transcription is dependent on an adequate GH secretion, and in many tissues, it occurs independent of GH. We propose that GH may be a prohormone, rather than a hormone, since in many tissues and organs, it is proteolytically cleaved in a tissue-specific manner giving origin to shorter GH forms whose activity is still unknown.

Growth hormone pathways signaling for cell proliferation and survival in hippocampal neural precursors from postnatal mice.

BackgroundAccumulating evidence suggests that growth hormone (GH) may play a major role in the regulation of postnatal neurogenesis, thus supporting the possibility that it may be also involved in promoting brain repair after brain injury. In order to gain further insight on this possibility, in this study we have investigated the pathways signaling the effect of GH treatment on the proliferation and survival of hippocampal subgranular zone (SGZ)-derived neurospheres.ResultsOur results demonstrate that GH treatment promotes both proliferation and survival of SGZ neurospheres. By using specific chemical inhibitors we have been also able to demonstrate that GH treatment promotes the activation of both Akt-mTOR and JNK signaling pathways, while blockade of these pathways either reduces or abolishes the GH effects. In contrast, no effect of GH on the activation of the Ras-ERK pathway was observed after GH treatment, despite blockade of this signaling path also resulted in a significant reduction of GH effects. Interestingly, SGZ cells were also capable of producing GH, and blockade of endogenous GH also resulted in a decrease in the proliferation and survival of SGZ neurospheres.ConclusionsAltogether, our findings suggest that GH treatment may promote the proliferation and survival of neural progenitors. This effect may be elicited by cooperating with locally-produced GH in order to increase the response of neural progenitors to adequate stimuli. On this view, the possibility of using GH treatment to promote neurogenesis and cell survival in some acquired neural injuries may be envisaged.

Growth hormone treatment enhances the functional recovery of sciatic nerves after transection and repair

Introduction: Although nerves can spontaneously regenerate in the peripheral nervous system without treatment, functional recovery is generally poor, and thus there is a need for strategies to improve nerve regeneration. Methods: The left sciatic nerve of adult rats was transected and immediately repaired by epineurial sutures. Rats were then assigned to one of two experimental groups treated with either growth hormone (GH) or saline for 8 weeks. Sciatic nerve regeneration was estimated by histological evaluation, nerve conduction tests, and rotarod and treadmill performance. Results: GH‐treated rats showed increased cellularity at the lesion site together with more abundant immunoreactive axons and Schwann cells. Compound muscle action potential (CMAP) amplitude was also higher in these animals, and CMAP latency was significantly lower. Treadmill performance increased in rats receiving GH. Conclusion: GH enhanced the functional recovery of the damaged nerves, thus supporting the use of GH treatment, alone or combined with other therapeutic approaches, in promoting nerve repair. Muscle Nerve, 2012

Recovery from neurological sequelae secondary to oncological brain surgery in an adult growth hormone-deficient patient after growth hormone treatment.

OBJECTIVE To report an unusual case of significant neurological recovery in a 26-year-old growth hormone-deficient female patient with significant neurological sequelae resulting from brain surgery at 11 years of age. DESIGN Case report. RESULTS Most of the neurological sequelae present at admission recovered after 8 months of combined growth hormone administration and kinesitherapy/speech therapy. These include an increase in tongue size and mobility and in the amount and quality of saliva, improvement in vocal cords function, recovery of oesophageal peristalsis and disappearance of sleep apnoea. CONCLUSION Since the patient had undergone intensive physical rehabilitation for a 15-year period with no significant improvement, it is tempting to speculate that the correction of growth hormone deficiency improved her rehabilitation. Therefore, we propose that growth hormone treatment, combined with the adequate kinesitherapy, may be a useful therapy for effective recovery from some neurological deficits in patients with growth hormone deficiency.

Brain Recovery after a Plane Crash: Treatment with Growth Hormone (GH) and Neurorehabilitation: A Case Report.

The aim of this study is to describe the results obtained after growth hormone (GH) treatment and neurorehabilitation in a young man that suffered a very grave traumatic brain injury (TBI) after a plane crash. Methods: Fifteen months after the accident, the patient was treated with GH, 1 mg/day, at three-month intervals, followed by one-month resting, together with daily neurorehabilitation. Blood analysis at admission showed that no pituitary deficits existed. At admission, the patient presented: spastic tetraplegia, dysarthria, dysphagia, very severe cognitive deficits and joint deformities. Computerized tomography scanners (CT-Scans) revealed the practical loss of the right brain hemisphere and important injuries in the left one. Clinical and blood analysis assessments were performed every three months for three years. Feet surgery was needed because of irreducible equinovarus. Results: Clinical and kinesitherapy assessments revealed a prompt improvement in cognitive functions, dysarthria and dysphagia disappeared and three years later the patient was able to live a practically normal life, walking alone and coming back to his studies. No adverse effects were observed during and after GH administration. Conclusions: These results, together with previous results from our group, indicate that GH treatment is safe and effective for helping neurorehabilitation in TBI patients, once the acute phase is resolved, regardless of whether or not they have GH-deficiency (GHD).

Effects of recombinant growth hormone replacement and physical rehabilitation in recovery of gross motor function in children with cerebral palsy.

Cerebral palsy is an important health issue that has a strong socioeconomic impact. There is no cure for cerebral palsy, and therapeutic approaches only report small benefits for affected people. In this study we assessed the effects of growth hormone treatment (0.3 μg/kg/day) combined with physical rehabilitation in the recovery of gross motor function in children with growth hormone deficiency and cerebral palsy (four males and six females, mean age 5.63 ± 2.32 years) as compared with that observed in a similar population of cerebral palsy children (five males, five females, mean age 5.9 ± 2.18 years) without growth hormone deficiency treated only with physical rehabilitation for two months. The Gross Motor Function Measure (GMFM-88) and Modified Ashworth Scale were performed before commencing the treatment and after completion thereof. In children with cerebral palsy and growth hormone deficiency, Dimension A (P < 0.02), dimension B (P < 0.02), and dimension C (P < 0.02) of the GMFM-88, and the total score of the test (P < 0.01) significantly improved after the treatment; dimension D and dimension E did not increase, and four of five spastic patients showed a reduction in spasticity. However, in children with cerebral palsy and without growth hormone deficiency, only the total score of the test improved significantly after the treatment period. This indicates that growth hormone replacement therapy was responsible for the large differences observed between both groups in response to physical rehabilitation. We propose that the combined therapy involving growth hormone administration and physical rehabilitation may be a useful therapeutic approach in the recovery of gross motor function in children with growth hormone deficiency and cerebral palsy.

Learning and Memory Recoveries in a Young Girl Treated with Growth Hormone and Neurorehabilitation

Background—To describe the results obtained after treating a non growth hormone-deficient 10-year-old girl who suffered asphyxia during delivery, resulting in important cognitive deficits, with growth hormone (GH) and neurorehabilitation. Methods—GH was administered (mg/day) at doses of 0.5 over three months followed by 0.9, every two weeks over three months, and then alternating 1.2 three days/week and 0.3 two days/week. Neurorehabilitation consisted of daily sessions of neurostimulation, speech therapy, occupational therapy and auditive stimulation. Treatment lasted nine months. Results—Scores obtained in all the areas treated showed that, at discharge, the patient clearly increased her cognitive abilities, memory and language competence index; her intelligence quotient score increased from 51 to 80, and the index of functional independence measure reached a value of 120 over 126 (maximal value). Conclusions—This case suggests that GH administration may play a role in improving cognitive deficits during neurorehabilitation in children with brain damage suffered during delivery. This agrees with the known effects of GH on cognition.