Biomedical subjects

J Guan

Publications and source records attributed to J Guan.

At least 55 records · Page 3Linked to original sources

PubMed2001

Effect of aggregate size and structure on specific resistance of biosolids filter cakes.

Investigation of the specific resistance to filtration of biosolids modified by cationic polymer addition reveals a dependence on both size and structure of the resulting biosolids flocs. This dependence is reasonably described by a modified form of the Carman-Kozeny equation and reveals that effects of differences in floc structure on cake resistance are most marked for flocs of small size. Conversely, effects of differences in floc size are most significant when flocs are more compact.

Filtration↗

PubMed2001

[Changes of segmental motion after spinal manipulation in patients with lumbar intervertebral disc protrusion].

OBJECTIVE: To explore the effect of manipulation on segmental motion of lumbar vertebra and the clinical significance before and after treatment, and evaluation with charge couple device (CCD) measurement system. METHODS: CCD and dynamic radiography were conducted in 30 patients before and after treated by manipulation or other conservative therapy, analysis and comparisons in segmental motion ranges of flexion-extension and lateral bending, correlation between data of CCD system and radiography as well as characteristics of lumbar vertebral function recovery after manipulation were performed. RESULTS: Certain correlation between data of CCD and radiography was shown by linear correlation test (r = 0.42-0.72, P < 0.05-0.01). Paired t test showed that the lower lumbar segmental flexion-extension function was significantly recovered (t = 2.26-2.61, P < 0.05-0.01) after manipulation, but the recovery on other segments was insignificant. CONCLUSION: The special designed CCD system is of important clinical significance in assessing segmental lumbar vertebral function. Lower lumbar vertebral flexion-extention functional state is a crucial criterium for evaluation of manipulative therapy in lumbar intervertebral disc protrusion.

Adult↗

PubMed2001

[Survivin--a new tumor-specific anti-apoptosis factor].

Survivin (SVV) is a new member of IAP-family (inhibitor of apoptosis, IAP) proteins. It can inhibit apoptosis induced by a variety of factors, and plays important roles during mitosis and cytokinesis of cells. Studies indicated that it is a tumor-specific anti-apoptosis factor. Survivin is expressed during embryonal development but lacks expression in terminally differentiated adult tissues. Interestingly, it becomes reexpressed in transformed cell lines and in a variety of human tumors. Its overexpression is prognostic of tumors and is implicated in the resistance to chemotherapy of tumor cells. SVV may be a new and widely applicable target for gene- and protein-based therapy of tumors.

Apoptosis↗

PubMed2000

Homologous recombination as a potential target for caffeine radiosensitization in mammalian cells: reduced caffeine radiosensitization in XRCC2 and XRCC3 mutants.

The radiosensitizing effect of caffeine has been associated with the disruption of multiple DNA damage-responsive cell cycle checkpoints, but several lines of evidence also implicate inhibition of DNA repair. The role of DNA repair inhibition in caffeine radiosensitization remains uncharacterized, and it is unknown which repair process, or lesion, is affected. We show that a radiosensitive cell line, mutant for the RAD51 homolog XRCC2 and defective in homologous recombination repair (HRR), displays significantly diminished caffeine radiosensitization that can be restored by expression of XRCC2. Despite the reduced radiosensitization, caffeine effectively abrogates checkpoints in S and G2 phases in XRCC2 mutant cells indicating that checkpoint abrogation is not sufficient for radiosensitization. Another radiosensitive line, mutant for XRCC3 and defective in HRR, similarly shows reduced caffeine radiosensitization. On the other hand, a radiosensitive mutant (irs-20) of DNA-PKcs with a defect in non-homologous end-joining (NHEJ) is radiosensitized by caffeine to an extent comparable to wild-type cells. In addition, rejoining of radiation-induced DNA DSBs, that mainly reflects NHEJ, remains unaffected by caffeine in XRCC2 and XRCC3 mutants, or their wild-type counterparts. These observations suggest that caffeine targets steps in HRR but not in NHEJ and that abrogation of checkpoint response is not sufficient to explain radiosensitization. Indeed, immortalized fibroblasts from AT patients show caffeine radiosensitization despite the checkpoint defects associated with ATM mutation. We propose that caffeine radiosensitization is mediated by inhibition of stages in DNA DSB repair requiring HRR and that checkpoint disruption contributes by allowing these DSBs to transit into irreparable states. Thus, checkpoints may contribute to genomic stability by promoting error-free HRR.

Animals↗

PubMed2000

N-terminal tripeptide of IGF-1 (GPE) prevents the loss of TH positive neurons after 6-OHDA induced nigral lesion in rats.

The effect of the N-terminal tripeptide of insulin-like growth factor (IGF)-1, glycine-proline-glutamate (GPE), as a neuroprotective agent for nigro-striatal dopaminergic neurons was examined in the present study using a rat model of Parkinson's disease. A unilateral nigro-striatal lesion was induced in rats by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle (MFB). GPE (3 microgram) or its vehicle was administered intracerebroventricularly (i.c.v.) 2 h after the 6-OHDA lesion. Tyrosine-hydroxylase (TH) immunohistochemistry in the substantia nigra compacta (SNc) and the striatum were examined 2 weeks after the lesion. Following 6-OHDA injection, the number of TH immunopositive neurons in the ipsilateral SNc was reduced. The density of TH immunostaining was also reduced in the ipsilateral SNc and the striatum. Treatment with a single dose of GPE (n=9) significantly prevented the loss of TH immunopositive neurons (p<0. 001) and restored the TH immunoreactivity in both the SNc and the striatum compared with the vehicle control group (n=9, p<0.001). The results suggest that GPE showed promise as a potential treatment for Parkinson's disease.

Animals↗

PubMed2000

1,3-Diarylcycloalkanopyrazoles and diphenyl hydrazides as selective inhibitors of cyclooxygenase-2.

Novel 1,3-diarylcycloalkanopyrazoles 1, and diphenyl hydrazides 2 were identified as selective inhibitors of cyclooxygenase-2. The 1,3-diaryl substitution pattern of the pyrazole ring in 1 differentiates these compounds from most of the known selective COX-2 inhibitors that contain two aryl rings at the adjacent positions on a heterocyclic or a phenyl ring. Similarly, the two phenyl rings in 2 are also separated by three atoms. SAR of both phenyl rings in 1 and 2, and the aliphatic ring in 1 will be discussed.

Azides↗

PubMed2000

Targeting of human eNOS promoter to the Hprt locus of mice leads to tissue-restricted transgene expression.

Phenotypic heterogeneity of the endothelium arises from cell type-specific differences in gene expression. An understanding of the mechanisms that underlie differential gene expression would provide important insight into the molecular basis of vascular diversity. In standard transgenic assays, multiple copies of heterologous DNA cassettes are randomly integrated into the mouse genome, resulting in significant line-to-line variation in expression. To overcome these limitations, we have targeted a single copy of a transgene that contains 1,600 bp of the human endothelial nitric oxide synthase (eNOS) promoter coupled to the LacZ reporter gene to the X-linked hypoxanthine phosphoribosyltransferase (Hprt) locus of mice by homologous recombination. The transgene was inserted in either of the orientations relative to that of the Hprt gene. In mice derived from multiple embryonic stem (ES) cell clones, the expression pattern was limited to a subset of endothelial cells, cardiomyocytes, and vascular smooth muscle cells. These findings suggest that Hprt locus targeting is a feasible tool for studying endothelial cell-restricted gene regulation.

Animals↗

PubMed2000

Unique biochemical, cytotoxic, and antitumor activity of camptothecin and 4beta-amino-4'-O-demethylepipodophyllotoxin conjugates.

Two compounds having a camptothecin (CPT) analog conjugated to the 4beta-amino-4'-O-demethylepipodophyllotoxin analog were evaluated for their biochemical and biological activities. W1[camptothecin-(para)-4beta-amino-4'-O-demethylepipodophyllotoxin] had no activity against topoisomerase II (TOP II), but inhibited topoisomerase I (TOP I) with an IC(50) value 2-fold higher than CPT. W2 [camptothecin-(ortho)-4beta-amino-4'-O-demethylepipodophyllotoxin] had inhibitory activity against TOP I and TOP II with IC(50) values 1.5-fold higher than either CPT or etoposide (VP-16). Both conjugates had similar cytotoxicity against the KB cell line, although the protein-linked DNA breaks (PLDBs) generated by W2 in KB cells were about 4-fold more than those of W1. No cross-resistance with the two conjugates was seen in a VP-16-resistant KB subline, which showed down-regulation of TOP II and overexpression of the multiple drug resistance-associated protein, or in a vincristine-resistant KB subline with overexpression of gp-170/mdr-1. The CPT-resistant KB variant (KB CPT 100), which has a reduction in TOP I content and another mechanism that occurs post-PLDB formation, was partially resistant to both compounds. W1 was not affected by this post-PLDB resistance mechanism. Cell cycle analysis demonstrated that W1 and W1 had similar cell cycle effects on KB and KB CPT 100 cells, which accumulated in S-phase upon drug treatment. These results suggested that W1 and W2 exerted their cytotoxicity through TOP I. In CPT-resistant cells, however, an unidentified target also may be involved in the cytotoxic action of W1 and TOP II may still be a target for W1. In vivo, W1 was more effective against the growth of human prostate cancer cells in nude mice than VP-16, CPT, or W2. Given its antitumor activity and unique biochemical mechanism of action, W1 warrants exploration as an antitumor compound.

Animals↗

PubMed2000

The catalytic subunit DNA-dependent protein kinase (DNA-PKcs) facilitates recovery from radiation-induced inhibition of DNA replication.

Exposure of cells to ionizing radiation inhibits DNA replication in a dose-dependent manner. The dose response is biphasic and the initial steep component reflects inhibition of replicon initiation thought to be mediated by activation of the S-phase checkpoint. In mammalian cells, inhibition of replicon initiation requires the ataxia telagiectasia mutated ( ATM ) gene, a member of the phosphatidyl inositol kinase-like (PIKL) family of protein kinases. We studied the effect on replicon initiation of another member of the PI-3 family of protein kinases, the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) by measuring either total DNA synthesis, or size distribution of nascent DNA using alkaline sucrose gradient centrifugation. Exposure of human cells proficient in DNA-PKcs (HeLa or M059-K) to 10 Gy inhibited replicon initiation in a time-dependent manner. Inhibition was at a maximum 1 h after irradiation and recovered at later times. Similar treatment of human cells deficient in DNA-PKcs (M059-J) inhibited replicon initiation to a similar level and with similar kinetics; however, no evidence for recovery, or only limited recovery, was observed for up to 8 h after irradiation. In addition a defect was observed in the maturation of nascent DNA. Similarly, a Chinese hamster cell line deficient in DNA-PKcs (irs-20) showed little evidence for recovery of DNA replication inhibition up to 6 h after irradiation, whereas the parental CHO cells showed significant recovery and an irs-20 derivative expressing the human DNA-PKcs complete recovery within 4 h. Normal kinetics of recovery were observed in xrs-5 cells, deficient in Ku80; in 180BR cells, deficient in DNA ligase IV; as well as XR-1 cells, deficient in XRCC4, an accessory factor of DNA ligase IV. Since all these cell lines share the DNA double strand break rejoining defect of M059-J and irs20 cells, the lack of recovery of DNA replication in the latter cells may not be attributed entirely to the prolonged presence of unrepaired DNA dsb. We propose that DNA-PKcs, in addition to its functions in the rejoining of DNA dsb and in DNA replication, also operates in a pathway that in normal cells facilitates recovery of DNA replication after irradiation.

Animals↗

PubMed2000

Intracerebral transportation and cellular localisation of insulin-like growth factor-1 following central administration to rats with hypoxic-ischemic brain injury.

Insulin-like growth factor-1 (IGF-1) has been shown to be neuroprotective when administered centrally following hypoxic-ischemic (HI) brain injury. However, the cerebral distribution and site of action of IGF-1 after intracerebroventricular (i.c.v.) administration are not known. A unilateral HI brain injury was induced in adult rats by a modified Levine method. Either 3H-IGF-1 alone, or in combination with unlabelled IGF-1, was administered into the lateral ventricle 2 h after injury. The activity of 3H-IGF-1 signal in the potentially injured cortex was compared between two treatment groups using image analysis. The regional distribution and cellular localisation of 3H-IGF-1 were examined autoradiographically in potentially injured hemispheres at 0.5 and 6 h after administration. Tritiated IGF-1 was detected predominantly in the pia mater, perivascular spaces and subcortical white matter tracts 0.5 h after administration and decreased by 6 h (p<0.05). The signals associated with the perivascular spaces and pia mater were not blocked by unlabelled IGF-1, suggesting non-saturable binding in these brain areas. IGF-1 signal was co-localised with IGF binding protein (IGFBP)-2 immunostaining in the white matter tracts where the signal was blocked by unlabelled IGF-1, suggesting competitive association. IGF-1 signal associated with neurons and glia was maximal in the cerebral cortex and less in the CA1-2 subregion of the hippocampus which were blocked by unlabelled IGF-1 (p<0.05). The signals from cortical neurons did not decrease 6 h after administration, suggesting specific and persistent binding to these cells. Our results indicate that centrally administered IGF-1 can be translocated to neurons and glia via the perivascular circulation and the ependymal cell-white matter tract pathways.

Animals↗

PubMed2000

Degradation of heterotrimeric Galpha(o) subunits via the proteosome pathway is induced by the hsp90-specific compound geldanamycin.

One mechanism utilized by cells to maintain signaling pathways is to regulate the levels of specific signal transduction proteins. The compound geldanamycin (GA) specifically interacts with heat shock protein 90 (hsp90) complexes and has been widely utilized to study the role of hsp90 in modulating the function of signaling proteins. In this study, we used GA to demonstrate that levels of heterotrimeric Galpha subunits can be regulated through interactions with hsp90. In a dose-dependent manner, GA significantly reduced the steady state levels of endogenous Galpha(o) expression in two cell lines (PC12 and GH3) and had a similar effect on Galpha(o) transiently expressed in COS cells. Galpha(o) synthesis and degradation was studied in PC12 cells and in transiently transfected COS cells. (35)S labeling followed by immunoprecipitation demonstrated no effect of GA on the rate of Galpha(o) synthesis, but GA accelerated degradation of Galpha(o) in both PC12 cells and COS cells. The use of inhibitors, including lactacystin (a proteosome-specific inhibitor), suggests that Galpha(o) is predominantly degraded through the proteosome pathway. In vitro translated (35)S-labeled Galpha(o) could be detected in hsp90 immunoprecipitates, and this interaction did not require N-terminal myristoylation. Taken together, these results suggest that heterotrimeric Galpha(o) subunits are protected from degradation by interaction with hsp90 and that the interaction of Galpha subunits with heat shock proteins may be a general mechanism for regulating Galpha levels in the cell.

Animals↗

PubMed2000

Selective neuroprotective effects with insulin-like growth factor-1 in phenotypic striatal neurons following ischemic brain injury in fetal sheep.

Severe perinatal asphyxia can lead to injury and dysfunction of the basal ganglia. Post insult administration of insulin-like growth factor-1 is neuroprotective, particularly in the striatum. Insulin-like growth factor-1 is also known to be a neuromodulator of several types of striatal neurons. The striatum comprises various phenotypic neurons with a complex neurochemical anatomy and physiology. In the present study, we examined the specificity of neuronal rescue with insulin-like growth factor-1 on different striatal neurons. Bilateral brain injury was induced in near term fetal sheep by 30 min of reversible carotid artery occlusion. A single dose of 3 microg of insulin-like growth factor-1 was infused over 1 h into the lateral ventricle 90 min following ischemia. The histological and immunohistochemical outcome were examined after 4 days recovery using paraffin tissue preparations. Insulin-like growth factor-1 treatment (n = 11) significantly reduced the percentage of neuronal loss in the striatum compared with the vehicle treated group (n = 10, 28.3+/-5.1% vs 55.5+/-17.3%, P < 0.005). Immunohistochemical studies showed that ischemia resulted in a significant loss of calbindin-28kd, choline acetyltransferase, parvalbumin, glutamate acid decarboxylase, neuronal nitric oxide synthase and neuropeptide Y immunopositive neurons, compared with sham controls. Insulin-like growth factor-1 markedly prevented the loss of calbindin-28kd (n = 7, P < 0.05), choline acetyltransferase (n = 7, P < 0.05), neuropeptide Y (n = 7, P < 0.05), neuronal nitric oxide synthase (n = 8, P < 0.05) and glutamate acid decarboxylase (n = 9, P < 0.05) immunopositive neurons, but failed to protect parvalbumin (n = 6) immunopositive neurons. The present study indicates that the therapeutic effect of insulin-like growth factor-1 in the basal ganglia is selectively associated with cholinergic and some phenotypic GABAergic neurons. These data suggest a potential role for insulin-like growth factor-1 in preventing cerebral palsy due to perinatal asphyxia.

Animals↗

PubMed2000

The effect of aging on adaptive eye-hand coordination.

Perceptual-motor adaptability of older adults (65 and older) was assessed. Participants in two groups (younger, 20-36 years, and older, 67-87 years) pointed 100 times at a straight-ahead visual target while looking through laterally displacing prisms, with the hand visible early in the pointing movement. Aftereffect tests were administered after adaptation. Each group was then split into decay and readaptation subgroups in which respective treatments were given twice. After each treatment, aftereffect tests were readministered. Eye-hand total shift was significantly smaller for older participants, proprioceptive shift was not statistically smaller for older participants, and visual shift did not appear. Readaptation produced greater reduction in aftereffects than did decay; this effect was the same for both groups. The main conclusion is that perceptual-motor adaptability declines with advancing age.

Adult↗

PubMed2000

The window of opportunity for neuronal rescue with insulin-like growth factor-1 after hypoxia-ischemia in rats is critically modulated by cerebral temperature during recovery.

Insulin-like growth factor (IGF-1) is induced in damaged brain tissue after hypoxia-ischemia, and exogenous administration of IGF-1 shortly after injury has been shown to be neuroprotective. However, it is unknown whether treatment with IGF-1 delayed by more than a few hours after injury may be protective. Hypothermia after brain injury has been reported to delay the development of ischemic neuronal death. The authors therefore hypothesize that a reduction in the environmental temperature during recovery from hypoxia-ischemia could prolong the window of opportunity for IGF-1 treatment. Unilateral brain damage was induced in adult rats using a modified Levine model of right carotid artery ligation followed by brief hypoxia (6% O2 for 10 minutes). The rats were maintained in either a warm (31 degrees C) or cool (23 degrees C) environment for the first 2 hours after hypoxia. All rats were subsequently transferred to the 23 degrees C environment until the end of the experiment. A single dose of IGF-1 (50 microg) or its vehicle was given intracerebroventricularly at either 2 or 6 hours after hypoxia. Histologic outcome in the lateral cortex was quantified 5 days after hypoxia. Finally, cortical temperature was recorded from 1 hour before and 2 hours after hypoxia in separate groups of rats exposed to the "warm" and "cool" protocols. In rats exposed to the warm recovery environment, IGF-1 reduced cortical damage (P < 0.05) when given 2 hours but not 6 hours after insult. In contrast, with early recovery in the cool environment, a significant protective effect of IGF-1 in the lateral cortex (P < 0.05) was found with administration 6 hours after insult. In conclusion, a reduction in cerebral temperature during the early recovery phase after severe hypoxia-ischemia did not significantly reduce the severity of injury after 5 days' recovery; however, it markedly shifted and extended the window of opportunity for delayed treatment with IGF-1.

Animals↗

PubMed2000

The Egr-1 gene is induced by epidermal growth factor in ECV304 cells and primary endothelial cells.

The early growth response (Egr)-1 transcription factor serves to couple changes in the extracellular environment to alterations in gene expression. An understanding of the mechanisms that underlie Egr-1 gene regulation should provide important insights into how environmental signals are transduced by endothelial cells. The aim of the present study was to determine whether epidermal growth factor (EGF) induces Egr-1 expression in endothelial cells. In ECV304 cells, Egr-1 mRNA and protein levels were increased in response to EGF. In stable transfection assays, the 1,200-bp promoter of the mouse Egr-1 gene contained information for EGF response via a protein kinase C-independent, mitogen-activated protein kinase-dependent pathway. The endogenous Egr-1 gene was similarly responsive to EGF in primary human umbilical vein endothelial cells, human coronary artery endothelial cells, and rat fat pad endothelial cells, but not in bovine aortic endothelial cells, calf pulmonary artery endothelial cells, or PY-4-1 endothelial cells. Together, these results suggest that the Egr-1 gene is responsive to EGF in a subset of endothelial cells.

3T3 Cells↗

PubMed2000

Surface photo-grafting of polyurethane with 2-hydroxyethyl acrylate for promotion of human endothelial cell adhesion and growth.

Cytocompatible polyurethane (PU) surface was prepared by photo-grafting 2-hydroxyethyl acrylate (HEA) onto the membrane surface. Graft polymerization was conducted by combining the use of the photo-oxidation and irradiation grafting. PU membrane was photo-oxidized to introduce the hydroperoxide groups onto the surface, then the membrane, immersed previously in monomer solution, was irradiated under UV light. The ATR-FTIR spectra, element spectroscopy for chemical analysis (ESCA), scanning electron microscopy (SEM) and water contact angle characterized the grafted copolymers and verified the occurrence of graft polymerization. The results showed that UV irradiation could realize the graft polymerization effectively and the grafting was confined within the surface layer. The grafted membrane showed minimal surface morphology. Human umbilical vein endothelial (HUVE) cells were seeded on the grafted surface. The performance of the surface in cell attachment and growth correlated with the oxygen content and mainly the carbonyl content on the surface. Cells were spread more extensively and grew faster on the surface with a higher oxygen content.

Acrylates↗

PubMed2000

Pyk2 and FAK differentially regulate progression of the cell cycle.

We have previously identified FAK and its associated signaling pathways as a mediator of cell cycle progression by integrins. In this report, we have analyzed the potential role and mechanism of Pyk2, a tyrosine kinase closely related to FAK, in cell cycle regulation by using tetracycline-regulated expression system as well as chimeric molecules. We have found that induction of Pyk2 inhibited G(1) to S phase transition whereas comparable induction of FAK expression accelerated it. Furthermore, expression of a chimeric protein containing Pyk2 N-terminal and kinase domain and FAK C-terminal domain (PFhy1) increased cell cycle progression as FAK. Conversely, the complementary chimeric molecule containing FAK N-terminal and kinase domain and Pyk2 C-terminal domain (FPhy2) inhibited cell cycle progression to an even greater extent than Pyk2. Biochemical analyses indicated that Pyk2 and FPhy2 stimulated JNK activation whereas FAK or PFhy1 had little effect on it, suggesting that differential activation of JNK by Pyk2 may contribute to its inhibition of cell cycle progression. In addition, Pyk2 and FPhy2 to a greater extent also inhibited Erk activation in cell adhesion whereas FAK and PFhy1 stimulated it, suggesting a role for Erk activation in mediating differential regulation of cell cycle by Pyk2 and FAK. A role for Erk and JNK pathways in mediating the cell cycle regulation by FAK and Pyk2 was also confirmed by using chemical inhibitors for these pathways. Finally, we showed that while FAK and PFhy1 were present in focal contacts, Pyk2 and FPhy2 were localized in the cytoplasm. Interestingly, both Pyk2 and FPhy2 (to a greater extent) were tyrosine phosphorylated and associated with Src and Fyn. This suggested that they may inhibit Erk activation in an analogous manner as the mislocalized FAK mutant (&Dgr;)C14 described previously by competing with endogenous FAK for binding signaling molecules such as Src and Fyn. This model is further supported by an inhibition of endogenous FAK association with active Src by Pyk2 and FPhy2 and a partial rescue by FAK of Pyk2-mediated cell cycle inhibition.

Animals↗

PubMed2000

A role for the somatotropic axis in neural development, injury and disease.

This review article discusses the roles of the somatotropic axis in the growth and development of the normal central nervous system (CNS) and during recovery from brain injury. Classically, the actions of pituitary-derived growth hormone (GH) have been reported to be primarily mediated via the induction of hepatic insulin-like growth factor-I (IGF-I). GH receptors (GHRs), however, have now been identified in many body tissues and shown to have both endocrine and local actions, some of which are IGF-I independent. Within the brain, GHRs are widely located across a range of cellular phenotypes, yet little is known regarding their function or endogenous ligand. It is now becoming accepted that GH, like IGF-I, is integrally involved in the growth and development of the normal CNS. Following brain injury, IGF-I mRNA is induced, primarily within reactive microglia. The resultant IGF-I protein appears to have a dual role, first as an endogenous neurotropic and anti-apoptotic agent acting directly on stressed cells, and second as a prohormone for generation of the N-terminal tripeptide of IGF-I, glycine-proline-glutamate (GPE), and the resulting des-N-(1-3)-IGF-I, both of which have specific neuroprotective properties. Our work on deciphering the upstream regulators of injury-induced IGF-I has revealed that a GH-like substance is strongly upregulated after brain injury and specifically associated with stressed neurons and glia. Subsequent to this finding, GH administered centrally 2 hours after a hypoxic-ischemic brain injury in juvenile rats was found to provide significant neuroprotection, interestingly, in a spatiotemporal pattern distinct from the neuroprotection offered by IGF-I. The implications of these findings in regard to the growth, development and injury response of the CNS are discussed.

Aging↗