Insulin-like Growth Factor-1 (IGF-1) Improves both Neurological Motor and Cognitive Outcome Following Experimental Brain Injury

Saatman, Kathryn E.; Contreras, Patricia C.; Smith, Douglas H.; Raghupathi, Ramesh; McDERMOTT, Kelli L.; Fernandez, Seamus C.; Sanderson, Kristin L; Voddi, Madhu; McIntosh, Tracy K.

doi:10.1006/exnr.1997.6629

Cited by 173 publications

(124 citation statements)

References 68 publications

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“…Five animals died in the immediate post-injury period, producing an injury mortality of 18%, consistent with previous reports using the lateral FP brain injury model of moderate severity (Saatman et al, 1997).…”

Section: Resultssupporting

confidence: 90%

Selective temporal and regional alterations of Nogo-A and small proline-rich repeat protein 1A (SPRR1A) but not Nogo-66 receptor (NgR) occur following traumatic brain injury in the rat

Marklund

Fulp

Shimizu

et al. 2006

Experimental Neurology

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Axons show a poor regenerative capacity following traumatic central nervous system (CNS) injury, partly due to the expression of inhibitors of axonal outgrowth, of which Nogo-A is considered the most important. We evaluated the acute expression of Nogo-A, the Nogo-66 receptor (NgR) and the novel small proline-rich repeat protein 1A (SPRR1A, previously undetected in brain), following experimental lateral fluid percussion (FP) brain injury in rats. Immunofluorescence with antibodies against Nogo-A, NgR and SPRR1A was combined with antibodies against the neuronal markers NeuN and microtubule-associated protein (MAP)-2 and the oligodendrocyte marker RIP, while Western blot analysis was performed for Nogo-A and NgR. Brain injury produced a significant increase in Nogo-A expression in injured cortex, ipsilateral external capsule and reticular thalamus from days 1-7 post-injury (P < 0.05) compared to controls. Increased expression of Nogo-A was observed in both RIP-and NeuN positive (+) cells in the ipsilateral cortex, in NeuN (+) cells in the CA3 region of the hippocampus and reticular thalamus and in RIP (+) cells in white matter tracts. Alterations in NgR expression were not observed following traumatic brain injury (TBI). Brain injury increased the extent of SPRR1A expression in the ipsilateral cortex and the CA3 at all post-injury time-points in NeuN (+) cells. The marked increases in Nogo-A and SPRR1A in several important brain regions suggest that although inhibitors of axonal growth may be upregulated, the injured brain is also capable of expressing proteins promoting axonal outgrowth following TBI. KeywordsNogo-A; Nogo-66 receptor; Small proline-rich repeat protein 1A (SPRR1A); Traumatic brain injury; Oligodendrocytes

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Section: Resultssupporting

confidence: 90%

Selective temporal and regional alterations of Nogo-A and small proline-rich repeat protein 1A (SPRR1A) but not Nogo-66 receptor (NgR) occur following traumatic brain injury in the rat

Marklund

Fulp

Shimizu

et al. 2006

Experimental Neurology

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“…It has been suggested that an increase in the expression of the IGF-I gene or peripherally administered IGF-I plays an important role in the neurotrophic response after injury such as epilepsy or ischemia in the adult rat brain (Gluckman et al, 1992;Guan et al, 1993;Breese et al, 1996;Saatman et al, 1997;Tagami et al, 1997;Liu et al, 1998;Hughes et al, 1999). Several disorders are associated with GCL pathology.…”

Section: Potential Of Induced Neurogenesis In the Dentate Gyrusmentioning

confidence: 99%

Peripheral Infusion of IGF-I Selectively Induces Neurogenesis in the Adult Rat Hippocampus

et al. 2000

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In several species, including humans, the dentate granule cell layer (GCL) of the hippocampus exhibits neurogenesis throughout adult life. The ability to regulate adult neurogenesis pharmacologically may be of therapeutic value as a mechanism for replacing lost neurons. Insulin-like growth factor-I (IGF-I) is a growth-promoting peptide hormone that has been shown to have neurotrophic properties. The relationship between IGF-I and adult hippocampal neurogenesis is to date unknown. The aim of this study was to investigate the effect of the peripheral administration of IGF-I on cellular proliferation in the dentate subgranular proliferative zone, which contains neuronal progenitor cells, and on the subsequent migration and differentiation of progenitor cells within the GCL. Using bromodeoxyuridine (BrdU) labeling, we found a significant increase of BrdUimmunoreactive progenitors in the GCL after 6 d of peripheral IGF-I administration. To determine the cell fate in progenitor progeny, we characterized the colocalization of BrdUimmunolabeled cells with cell-specific markers. In animals treated with IGF-I for 20 d, BrdU-positive cells increased significantly. Furthermore, the fraction of newly generated neurons in the GCL increased, as evaluated by the neuronal markers Calbindin D 28K , microtubule-associated protein-2, and NeuN. There was no difference in the fraction of newly generated astrocytes. Thus, our results show that peripheral infusion of IGF-I increases progenitor cell proliferation and selectively induces neurogenesis in the progeny of adult neural progenitor cells. This corresponds to a 78 Ϯ 17% ( p Ͻ 0.001) increase in the number of new neurons in IGF-I-treated animals compared with controls. Key words: brain; rat; IGF-I; insulin-like growth factor-I; stem cell; progenitor cell; hippocampus; neurogenesis; stereologyMost CNS neurons are terminally differentiated and are, thus, not replaced after neuronal cell death. However, self-renewing cells with multilineage potential, designated stem cells or progenitor cells, have been identified in the adult mammalian brain

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“…Experimental and clinical efforts aimed at treating this significant health care issue have resulted in numerous therapeutic approaches such as, but not limited to, anti-inflammatory and anti-oxidative strategies [4,34,36,39,51,56,101], hypothermia [5,9,13,14,21,57], and the exogenous administration of neurotrophins [19,84,88]. Another line of research that has received significant attention as a potential treatment strategy is the administration of various pharmacologic agents targeting both specific and non-specific neurotransmitter systems in an attempt to restore neural activity that has been altered by TBI [2,25,44,[51][52][53][54][55].…”

Section: Introductionmentioning

confidence: 99%

Acute treatment with the 5-HT1A receptor agonist 8-OH-DPAT and chronic environmental enrichment confer neurobehavioral benefit after experimental brain trauma

Kline

Wagner

Westergom

et al. 2007

Behavioural Brain Research

101

166

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Acute treatment with the 5-HT 1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) or chronic environmental enrichment (EE) hasten behavioral recovery after experimental traumatic brain injury (TBI). The aim of this study was to determine if combining these interventions would confer additional benefit. Anesthetized adult male rats received either a cortical impact or sham injury followed 15 min later by a single intraperitoneal injection of 8-OH-DPAT (0.5 mg/kg) or saline vehicle (1.0 mL/kg) and then randomly assigned to either enriched or standard (STD) housing. Behavioral assessments were conducted utilizing established motor and cognitive tests on post-injury days 1-5 and 14-18, respectively. Hippocampal CA 1 /CA 3 neurons were quantified at 3 weeks. Both 8-OH-DPAT and EE attenuated CA 3 cell loss. 8-OH-DPAT enhanced spatial learning in a Morris water maze (MWM) as revealed by differences between the TBI+8-OH-DPAT+STD and TBI+VEHICLE+STD groups (P=0.0014). EE improved motor function as demonstrated by reduced time to traverse an elevated narrow beam in both the TBI+8-OH-DPAT+EE and TBI+VEHICLE +EE groups vs. the TBI+VEHICLE+STD group (P=0.0007 and P=0.0016, respectively). EE also facilitated MWM learning as evidenced by both the TBI+8-OH-DPAT+EE and TBI+VEHICLE+EE groups locating the escape platform quicker than the TBI+VEHICLE+STD group (P's<0.0001). MWM differences were also observed between the TBI+8-OH-DPAT+EE and TBI+8-OH-DPAT +STD groups (P=0.0004) suggesting that EE enhanced the effect of 8-OH-DPAT. However, there was no difference between the TBI+8-OH-DPAT+EE and TBI+VEHICLE+EE groups. These data replicate previous results from our laboratory showing that both a single systemic administration of 8-OH-DPAT and EE improve recovery after TBI and extend those findings by elucidating that the combination of treatments in this particular paradigm did not confer additional benefit. One explanation for the lack of an additive effect is that EE is a very effective treatment and thus there is very little room for 8-OH-DPAT to confer additional statistically significant improvement.

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Insulin-like Growth Factor-1 (IGF-1) Improves both Neurological Motor and Cognitive Outcome Following Experimental Brain Injury

Cited by 173 publications

References 68 publications

Selective temporal and regional alterations of Nogo-A and small proline-rich repeat protein 1A (SPRR1A) but not Nogo-66 receptor (NgR) occur following traumatic brain injury in the rat

Selective temporal and regional alterations of Nogo-A and small proline-rich repeat protein 1A (SPRR1A) but not Nogo-66 receptor (NgR) occur following traumatic brain injury in the rat

Peripheral Infusion of IGF-I Selectively Induces Neurogenesis in the Adult Rat Hippocampus

Acute treatment with the 5-HT1A receptor agonist 8-OH-DPAT and chronic environmental enrichment confer neurobehavioral benefit after experimental brain trauma

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